Carrot Potato Mash – My Bizzy Kitchen

By electricdiet / July 24, 2020


I’ve been doing Mariano’s pick up groceries since I am not on Day 11 of no results yet of my COVID test.  The sweet girl who did my shopping called me and said “we don’t have any one pound bag of carrots, can I substitute a pound of baby carrots?

Um, the question to that answer will always be “no thank you.”  Hamsters should be the only ones eating baby carrots – has!  

I told her to get me a bigger bag of bagged carrots if she could.  And when I got home and opened my grocery bag, I was gifted a FIVE POUND BAG of carrots.  So that’s how the carrot mash potatoes came to be – I am going to be making ALL THINGS CARROTS this week.

And as I type this, I may or may not have a batch of carrot cake pancakes waiting to be cooked.  Stay tuned for that.

Here is how I start out recipe developing.  I search existing recipes.  Um, turns out a lot of people went a very sweet route on mashed carrots adding maple syrup, cinnamon and brown sugar.  The carrots are already sweet, and that didn’t appeal to me at all.  I also thought I wanted to add potato to get it the consistency I wanted – like a mashed potato, not baby food carrot puree.  And I added crushed red pepper to balance the sweetness.

I peeled the potato and not the carrots.  The internet will tell you that peeling carrots strips away some of the nutrients.  But you are peeling such a thin layer, you aren’t really missing much by doing that.  I don’t find the carrot skin to have a bitter taste, so it boils down to personal preference.  Also, it’s a lot easier to just leave it on. 😀

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Carrot Potato Mash

A delicious side dish to beef, chicken or pork.  This carrot mash is slightly sweet with a hit of spicy from the crushed red pepper.

  • Author: Biz
  • Prep Time: 5
  • Cook Time: 20
  • Total Time: 25 minutes
  • Yield: 4 1x

Scale

Ingredients

  • 9 ounces potato, peeled and cut into cubes
  • 9 ounces carrot, cut into cubes
  • 1 tablespoon I Can’t Believe It’s Not Butter
  • 1/3 cup unsweetened almond milk
  • 1 teaspoon crushed red pepper (adjust to taste)
  • 1/2 teaspoon salt
  • 1/2 teaspoon pepper

Instructions

Put water in a stock pot.  Add potatoes and carrots.  Bring to a boil, cook for 5 minutes, remove from heat, put a lid on and let sit for 15 minutes.  The veggies will be fork tender.

Drain the veggies.  Add the butter, milk and seasonings and using a potato masher or stick blender, blend until smooth.  Add additional salt to taste.

Notes

On team purple each serving is 1 WW point – on team blue and green it is 2 WW points.

Nutrition

  • Serving Size: 3/4 cup
  • Calories: 89
  • Sugar: 3
  • Sodium: 99
  • Fat: 3
  • Saturated Fat: 1
  • Carbohydrates: 15
  • Fiber: 4
  • Protein: 2

The cut of steak I used is called a petite sirloin.  It’s closer to the rump so the internet will tell you that this cut is best for braising or roasting.  But it’s a steak – how do you braise a half pound of beef without cooking it to death?

So I treat it as I would a sirloin steak.  Some tips about cooking beef:  (1) let the steak come to room temperature before cooking.  Never put a cold steak into a hot pan.  (2) salt the beef within two minutes of cooking or after 40 minutes.  Within two minutes the salt still remains on the top and will sear into the meat.  Left longer than that, the salt starts to wick out the moisture in the beef.  After forty minutes though, the juices will have reabsorbed into the meat and you are good to go.  (3) cook with a meat thermometer.  I cooked my beef to 120 before removing it to rest.  That only took 3 minutes on one side and 2 minutes on the other to get to that temperature.

For my chimichurri sauce:  1 cup cilantro, 4 tablespoons grape seed oil, 2 tablespoons red wine vinegar, 4 cloves garlic, 1 teaspoon salt, 1 tablespoon sugar free orange marmalade.  Yes, you read that correctly – the orange marmalade balances the acidity of the cilantro and vinegar in the best way possible.  I suppose you could add honey, but I’ve not tried that.  I just put all the ingredients in a wide mouth mason jar and used a stick blender to blend.  You only need a teaspoon drizzled over the steak – 1 point on all WW plans and only 26 calories of delicious flavor.

 

So while I wish I was at a restaurant being served this meal with a nice glass of cabernet sauvignon, I had to make do and make it myself, and drink seltzer water since I am on Day 20 of #dryjuly.   If I were to have this steak dinner at a restaurant I am sure I would have spent $50 and up depending on where I went.  My dish cost me approximately $4.12.  Um, last time I checked, you can’t get McDonalds for that price.

I hope you try this potato mash.  Oh, and I realized people will ask me about the green beans and mushrooms.  I simply sauteed the mushrooms in avocado oil spray with salt and pepper.  The green beans I cooked in the microwave for 1 minute, then added them to the cast iron skillet when the steak came out to get a bit of char, and added salt and pepper.  That’s it!

This literally was about 20 minutes to make from beginning to end.  I hope you give this a try – tag me on Instagram if you do!

Until next time, Be Kind, Be Fearless, Have Hope – Love, Biz





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Easy Keto Lemon Bars Recipe

By electricdiet / July 22, 2020


These low-carb lemon bars are the perfect balance between sweet and lemony and they will leave you reaching for more! With a coconut flour crust and creamy filling, they are the perfect teatime treat. 

Four keto lemon bar squares on a white plate

If you love lemony, tangy desserts then this recipe is for you. Not only is this one of the best tasting keto desserts you can make but it’s so easy to prepare too. 

The creamy lemon filling and buttery shortcrust melt in your mouth and will leave you wondering how on earth something that tastes so rich and indulgent could possibly be low-carb! 

How to make keto lemon bars

Step 1: Measure out all the ingredients and preheat your oven to 325 ° F (160 ° C).

Step 2: Grease a 9”x 9” (23cm x 23cm) baking pan and line it with a strip of parchment paper (you don’t need to use the parchment strip if your pan has a removable base.)

Ingredients for the lemon bars on wooden board

Step 2: Combine the coconut flour, ground stevia, and salt in the bowl of a food processor by pulsing once or twice.

Step 3: Add the unsalted butter and pulse to combine, until it reaches a sandy consistency.

Preparing the coconut flour crust in a food processor

Step 4: Add the egg and vanilla extract to the food processor. Pulse to combine until the dough is well mixed and forms pea-sized pieces. There should be no dry areas in the dough. 

Step 5: Press the shortbread dough firmly into the prepared pan using the back of a glass or your hands. 

Dough pressed into a square pan

Step 6: Bake for 12-15 minutes, until the outer edges of the crust have just begun to brown. It should not be fully cooked at this stage as it will cook further once the filling has been added. Remove and leave the oven on.

Step 7: Mix together all the ingredients for the filling until completely smooth and pour over the baked crust. 

mixing all the filling ingredients in a large glass bowl

Step 8: Bake for 30 – 35 min. The lemon bars are done cooking once the filling stops moving if shaken slightly. Remove from the oven and allow the lemon bars to cool completely for at least an hour. Cut and serve when desired. 

Baked lemon bars in the pan

Tips for making the perfect lemon bars

Before you start preparing the shortcrust base of the lemon bars, remove the cream cheese from the refrigerator and let it sit out for at least 30 minutes before using it the filling. This makes sure that the cream cheese is easy to beat and won’t leave any lumps in your filling. 

One of the keys to getting perfect lemon bars is to make sure they cool completely before you decide to gobble them up. Let them cool enough that they are completely firm before eating. 

Storing the bars

Once the lemon bars have completely cooled, wrap them gently in plastic wrap so that they don’t dry out. They can be stored like this in the refrigerator for up to 4 days. 

baked lemon bars ready to serve

More healthy low-carb snack recipes

Great tasting keto treats are a great way to keep your blood sugar levels stable and satisfy your sweet tooth! Here are some of my favorite low-carb snacks to keep me going:

You can also check out my roundup of 10 diabetic cookie recipes for more snacking inspiration.

When you’ve tried this recipe for keto lemon bars, please don’t forget to let me know how you liked it and rate the recipe in the comments below!

Recipe Card

Easy Keto lemon bars

These low-carb lemon bars are the perfect balance between sweet and lemony and they will leave you reaching for more! With a coconut flour crust and creamy filling, they are the perfect teatime treat. 

Prep Time:15 minutes

Cook Time:45 minutes

Total Time:1 hour

Servings:9

Ingredients

For the shortbread crust:

Instructions

For the shortbread crust:

  • Preheat your oven to 325 ° F (160 ° C).

  • Grease a 9”x 9” (23cm x 23cm) baking pan and line it with a strip of parchment paper. You don’t need to use the parchment strip if your pan has a removable base.

  • Combine the coconut flour, ground stevia, and salt in the bowl of a food processor by pulsing once or twice.

  • Add the unsalted butter and pulse to combine until it reaches a sandy, well-mixed consistency.

  • Add the egg and vanilla extract to the bowl of the food processor and pulse to combine until the dough is well mixed comes together in small balls.

  • Add the dough to the prepared pan and press down firmly using your fingers or back of a glass.

  • Bake for 15 minutes, until the outer edges of the crust have just begun to brown. It will not be completely cooked at this point as it will bake further once the filling has been added. Remove and leave the oven on.

For the filling:

  • Mix together all the ingredients for the filling until completely smooth and pour over the baked crust. If the mixture has some lumps of butter or cream cheese, microwave for 1 – 2 minutes until you can mix until completely smooth.

  • Bake for 30 – 35 min. The lemon bars are done cooking if you shake the pan and the middle of the lemon bars shake slightly. Remove from the oven and allow the lemon bars to cool completely for at least an hour. Cut and serve when desired.

Recipe Notes

This recipe makes 9 servings.  The lemon bars can be stored like this in the refrigerator for up to 4 days.

Nutrition Info Per Serving

Nutrition Facts

Easy Keto lemon bars

Amount Per Serving

Calories 322 Calories from Fat 271

% Daily Value*

Fat 30.1g46%

Saturated Fat 18.5g93%

Polyunsaturated Fat 0.7g

Monounsaturated Fat 4.3g

Cholesterol 160mg53%

Sodium 129.6mg5%

Potassium 55.7mg2%

Carbohydrates 8.1g3%

Fiber 4g16%

Sugar 1.6g2%

Protein 5.2g10%

Net carbs 4.1g

* Percent Daily Values are based on a 2000 calorie diet.

Course: Dessert

Cuisine: American

Keyword: Keto Lemon Bars, low carb bars



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Cold Avocado Soup Recipe – 5-Ingredient Cold Cucumber Avocado Soup

By electricdiet / July 20, 2020


Cold Avocado Soup Recipe For Amazing Cold Cucumber Avocado Soup

If you like a refreshing starter, wait until you try this simple cold avocado soup recipe.  Two summer favorites, avocado and cucumber, are combined to create an amazing simple cold cucumber avocado soup recipe. This creamy avocado soup will be a favorite and this Avocado Cucumber Soup from Eating Well Through Cancer is wonderful for so many reasons.  An easy recipe for cancer patients, this cold cucumber soup is soothing and satisfying.  However, it isalso perfect for anyone who desires a light refreshing and delicious cold cucumber soup.

Cold Cucumber Avocado Soup
Creamy avocados and cucumbers pair together for the best cold avocado soup ever. This cold cucumber soup has great flavor and makes the best cold soup recipe. Most importantly, the recipes takes minutes to make.

    Servings6 (3/4 cup) servings

    Ingredients

    • 1


      large avocadopeeled, pitted, and halved

    • 2


      cucumberspeeled, seeded, and halved

    • 1cup


      or vegetable broth or low-sodium fat-free chicken

    • 1cup


      fat-free evaporated milk

    • 2tablespoons


      lemon juice



    • salt and pepper to taste

    Instructions
    1. In blender or food processor, blend avocado, cucumbers, broth, evaporated milk, and lemon juice until smooth. Season to taste. Refrigerate, covered, until chilled.


    2. If soup is too thick, gradually add more broth or evaporated milk.

    Recipe Notes

    Per Serving: Calories 99, Calories from fat 46%, Fat 5 g, Saturated Fat 1 g, Cholesterol 2 mg, Sodium 64 mg, Carbohydrate 10 g, Dietary Fiber 3 g, Sugars 7 g, Protein 5 g, Diabetic Exchanges: 1 vegetable, 1/2 fat-free milk, 1 fat

    Terrific Tip: To easily seed cucumbers: cut in half and run a knife or spoon down the center of the cucumber to scrape out the seeds.

    Nutrition Nugget: Avocados contain healthy unsaturated fats that help your body absorb and use vitamins, as well as help to maintain cell membranes.

    You Will Love These Gadgets To Make Cold Avocado Soup Recipe

    Avocado slicer, 3 In 1 Avocado Slicer Avocado CutterAvocado slicer, 3 In 1 Avocado Slicer Avocado CutterAvocado slicer, 3 In 1 Avocado Slicer Avocado CutterMSC International 33005 CLEAR COVER AVOCADO POD, GreenMSC International 33005 CLEAR COVER AVOCADO POD, GreenMSC International 33005 CLEAR COVER AVOCADO POD, GreenCuisinart CSB-75BC Smart Stick 200 Watt 2 Speed Hand BlenderCuisinart CSB-75BC Smart Stick 200 Watt 2 Speed Hand BlenderCuisinart CSB-75BC Smart Stick 200 Watt 2 Speed Hand Blender

    Whip Up 5-Ingredient Cold Avocado Soup Recipe In 5 Minutes

    This cold avocado soup recipe is in Holly’s cancer cookbook, however, it will quickly become a daily favorite.  Serve this recipe for lunch with a sandwich. On a hot day, there is nothing better!  You can even top it with a dollop of yogurt or some salsa for a little zing. Holly has even had parties and served a cup of this chilled avocado soup as an appetizer in a punch cup or demi tasse.  Everyone always really enjoys it.

    What’s great about Eating Well Through Cancer cookbook is it contains healthy easy recipes for everyone.  As you see, this cold cucumber soup recipe is great for cancer patients but it is also refreshing on a hot summer day!

    Delicious Cookbooks To Highlight Diabetic Recipes

    This wonderful 5-ingredient creamy avocado soup is also an easy diabetic recipe!  Remember, eating recipes in Holly’s cookbooks highlighted as simple diabetic recipes means it is the healthiest way to eat.  These cookbooks contain a “D” to highlight diabetic recipes!

    EATING WELL TO FIGHT ARTHRITIS: 200 easy recipes and practical tips to help REDUCE INFLAMMATION and EASE SYMPTOMSEATING WELL TO FIGHT ARTHRITIS: 200 easy recipes and practical tips to help REDUCE INFLAMMATION and EASE SYMPTOMSEATING WELL TO FIGHT ARTHRITIS: 200 easy recipes and practical tips to help REDUCE INFLAMMATION and EASE SYMPTOMSHolly Clegg's trim&TERRIFIC KITCHEN 101: Secrets to Cooking Confidence: Cooking Basics Plus 150 Easy Healthy RecipesHolly Clegg’s trim&TERRIFIC KITCHEN 101: Secrets to Cooking Confidence: Cooking Basics Plus 150 Easy Healthy RecipesHolly Clegg's trim&TERRIFIC KITCHEN 101: Secrets to Cooking Confidence: Cooking Basics Plus 150 Easy Healthy RecipesEating Well Through Cancer: Easy Recipes & Tips to Guide you Through Treatment and Cancer PreventionEating Well Through Cancer: Easy Recipes & Tips to Guide you Through Treatment and Cancer PreventionEating Well Through Cancer: Easy Recipes & Tips to Guide you Through Treatment and Cancer Prevention

    Get All of Holly’s Healthy Easy Cookbooks

    The post Cold Avocado Soup Recipe – 5-Ingredient Cold Cucumber Avocado Soup appeared first on The Healthy Cooking Blog.



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    Blood Flow in the Pancreatic Islet: Not so Isolated Anymore

    By electricdiet / July 18, 2020


    The pancreatic islet is a highly vascularized endocrine mini-organ that depends on blood supply to function efficiently. As blood flows through islet capillaries reaching different endocrine cell types, it significantly impacts nutrient sensing, paracrine communication, and the final hormonal output. Thus, any change in blood flow, either induced physiologically (e.g., nervous input) or as a result of pathological changes (e.g., fibrosis), could affect islet function. It is not a stretch to state that the way the islet vasculature is arranged anatomically and regulated functionally must have consequences for glucose homeostasis.

    Despite its potential impact for islet function, interest in the islet vasculature has been sporadic and is certainly not equal to that professed to the cells it serves. Still, there has been a substantive research effort in this arena. From beautiful scanning electron images of corrosion casts (1) to creative physiological experiments using perfused pancreases (2) and microbeads (3), investigators have employed various approaches to study the microcirculation of the islet. The results of these studies provided structural and functional insight but also raised questions. To settle a debate that had started in the mid-1960s, a group of prominent islet biologists decided to meet in 1996 to review existing notions about islet blood flow and “agreed to disagree” that there were three models (4). In model 1, non–β-cells are perfused before β-cells, allowing other endocrine cells to influence β-cells located downstream. In model 2, β-cells are perfused before the other endocrine cells and thus dominate islet function. In model 3, there is no apparent order of perfusion, but blood flows from the afferent to the efferent pole of the islet. The three flow patterns were confirmed more recently in in vivo studies in mice (5). Incidentally, the hierarchical organization based on blood flow may be possible in the mouse islet with its mantle versus core organization, but this scenario is highly unlikely in the desegregated human islet.

    Their differences notwithstanding, all three models assumed that the islet microcirculation is self-contained, with each islet having its own vascular network comprising feeding arterioles, a glomerulus-like capillary net, and dedicated venous drainage (Fig. 1). This arrangement allows islet blood flow to be regulated independently from that of the exocrine pancreas. This notion is now being challenged by hot-off-the-press findings appearing in this issue of Diabetes. In their study, Dybala et al. (6) used intravital imaging of the exteriorized mouse pancreas to track individual red blood cells moving through islet capillaries in real time. In these technically challenging experiments, the authors followed red blood cells as they exited and entered the islet and found that blood flow is bidirectional and continuously integrated with that of the exocrine pancreas at multiple locations. The idea that islets, in particular smaller islets, could be incorporated into the exocrine capillary system is not completely new (7), but in their study, Dybala et al. moved anatomical guesswork into real-time in vivo physiology to show directly that the islet microcirculation is open and not isolated from that of the surrounding exocrine tissue.

    Figure 1
    Figure 1

    Cartoons depicting three different models of blood flow in the pancreas. Until recently, the microcirculation of the islet was considered to be independent of that of the surrounding exocrine tissues (left). In an article published in this issue of Diabetes, Dybala et al. (6) now show that the circulation of the islet is integrated with that of the exocrine tissue, with blood flowing bidirectionally between both compartments (center). In a more sophisticated model, regulatory elements such as nervous input and vascular gates can be incorporated into this scheme to allow for local control of blood flow (right).

    The authors not only produced astonishingly detailed images of the pancreas vasculature but were further able to measure the basal velocity of individual red blood cells. The average speeds were similar inside and outside the islet, contradicting the prevalent view that islet blood flow is 5–10 times higher than in exocrine tissues. Because in vivo recordings of capillary blood flow are not yet possible in the human pancreas, the authors could only obtain structural data for human islets. The results are in line with previous observations made on corrosion casts that islets in the human pancreas are connected with the exocrine tissue through insulo-acinar portal vessels (1). Blood flow in the human islet can be expected to be integrated with its surroundings, as its vasculature already shows less of the tortuosity typical of the mouse islet vasculature (8,9). It is difficult to tell apart endocrine from exocrine regions based on vascular architecture in human pancreas sections. In addition, human islets do not have distinctive boundaries such as a capsule, which eliminates another barrier for full integration into the pancreatic vascular network.

    The model proposed by Dybala et al. (6) still requires experimental confirmation by peers in the field before it becomes the new canon (Fig. 1). Nevertheless, from a physiological point of view, it makes sense that blood supply to endocrine and exocrine compartments is integrated. Secretion of digestive enzymes and insulin is simultaneously activated when nutrients need to be absorbed (i.e., the fed state), which requires coordinated increases in blood perfusion to both regions. The intimate relationship between islets and acinar tissues is evident in findings showing that diabetes is often associated with abnormal pancreatic exocrine function (10) and that pancreases of individuals at risk for or with type 1 diabetes are smaller (11). If these compartments are integrated through their vasculature, then acinar tissues should be exposed to high concentrations of islet secretory products, such as insulin, and vice versa. Indeed, insulin has been shown to regulate exocrine function by affecting protein biosynthesis and zymogen discharge, in particular of amylase (12). In general, however, there is relatively little interest in understanding how the exocrine and endocrine tissues of the pancreas influence each other. In view of the results shown here, the biology of the endocrine pancreas (studied by endocrinologists) should no longer be studied separately from that of the exocrine pancreas (the focus of gastroenterologists).

    If endocrine and exocrine regions are really this integrated, is there still a chance for blood flow to be regulated selectively? Blood flow in the islet was proposed to be controlled by external gates at the level of the arteriole as well as by internal gates at the level of capillaries (4). These internal gates were described in early in vivo microscopy studies as “bulging endothelial cells” within islet capillaries that could influence the velocity and volume of blood flowing through capillaries (13). These internal gates are now known to be pericytes capable of changing islet capillary diameter and blood flow in response to increased β-cell activity or sympathetic nervous input (14). Thus, by responding to local and neural signals, the islet vasculature can alter blood flow selectively (Fig. 1). It is likely that similar mechanisms exist in acinar regions. Thus, we can imagine a scenario in which the perfusion of endocrine and exocrine compartments is regulated conjointly at the level of the pancreatic lobe while allowing for local control without the need for separate circulations. This should make everyone happy.

    Article Information

    Funding. This work was supported by National Institutes of Health grants K01DK111757 (J.A.), National Institute of Diabetes and Digestive and Kidney Diseases–supported Human Islet Research Network (UC4DK104162, New Investigator Pilot Award to J.A.), R01DK084321 (A.C.), R01DK111538 (A.C.), R01DK113093 (A.C.), U01DK120456 (A.C.), R33ES025673 (A.C.), and R21ES025673 (A.C.), and The Leona M. and Harry B. Helmsley Charitable Trust grants G-2018PG-T1D034 and G-1912-03552 (A.C.).

    Duality of Interest. No potential conflicts of interest relevant to this article were reported.



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    Shrimp Scampi Foil Packets (Oven or Grill)

    By electricdiet / July 16, 2020


    These shrimp scampi foil packets are healthy, flavorful, easy to cook, and a breeze to clean-up! Make them in the oven or on the grill for a quick and tasty meal.

    Cooked Shrimp Scampi in an open foil packet topped with bread crumbs and fresh parsley on a plate that's on top of a cutting board

    Are you always on the look-out for meals that feature easy clean-up? No one wants to finish a delicious dinner only to face a mountain of dishes in the kitchen.

    That’s why I love these shrimp scampi foil packets with artichoke hearts! The topping comes together in one pan, and everything else cooks right in the foil packets. How easy is that?

    And you can cook the shrimp packets either in the oven or on the grill. Choose whatever is most convenient for you!

    Did I mention that this shrimp dish is unbelievably delicious? It’s a little rich, but with just the right amount of herbs, lemon, and spices to balance it all out. And it’s low-carb, too!

    So the next time you’re craving shrimp or just want a meal that’s easy to cook AND clean-up, give this quick and tasty shrimp scampi recipe a try!

    How to make shrimp scampi foil packets

    This dish is so easy to make either in the oven or on the grill. Everything cooks right in the foil packets!

    Step 1: Heat a small skillet over medium heat.

    Step 2: Add 1 teaspoon of olive oil and the panko breadcrumbs, then cook, stirring frequently, until the panko is golden brown, about 3 minutes.

    Step 3: Transfer the mixture to a small bowl. Stir in the lemon zest, Parmesan, and garlic, then set aside.

    Step 4: Tear off 4 large sheets of heavy-duty foil, about 18 inches long each.

    Step 5: Place 1/4 of the artichoke hearts in the middle of each sheet of foil. Season with salt to taste, then top each with a thyme sprig, 3 to 4 lemon slices, and 1 teaspoon of butter.

    Step 6: In a large bowl, toss the shrimp with the crushed red pepper and garlic.

    Step 7: Add 1/4 of the shrimp mixture on top of the artichoke mixture on each sheet of foil. Drizzle each with 1 tablespoon of white wine and a 1/2 tablespoon of olive oil.

    Uncooked shrimp scampi in the foil packet ready to be wrapped and cooked

    Step 8: Bring the opposite sides of foil together and fold at least twice to seal, leaving a little headroom for the air to circulate. Then, fold the open sides over at least twice.

    Step 9: Cook the packets either directly on an oven rack for 15 to 20 minutes at 400°F or on a hot grill for about 10 minutes. The shrimp should be opaque when done.

    Step 10: Open the packets carefully and top with the toasted panko breadcrumbs and fresh parsley.

    Now all you have to do to clean up is toss the foil packets… after you enjoy your shrimp scampi, of course!

    What is shrimp scampi?

    In Italian, scampi refers to langoustines, which are tiny lobsters. They are traditionally cooked in a sauce that contains olive oil, white wine, and garlic.

    Since langoustines aren’t as common in the U.S., chefs started replacing them with shrimp in this recipe. And that’s how “shrimp scampi” came to be.

    There are so many flavor variations for this dish. It can be rich and buttery or light and herby. It might be served over pasta (or not). It may be lemony, spicy, or both. The possibilities are endless!

    The beauty of this version is that it’s a little bit rich, a little bit herby, a little bit spicy, and a little bit lemony. If you ask me, it’s really the best of all worlds!

    What to serve with this dish

    I like to choose sides that are light but with vibrant and fresh flavors to compliment this recipe.

    One of my favorites is a salad made with my homemade citrus vinaigrette. It adds a wonderful tanginess! And you can easily whip up the dressing while the shrimp are cooking.

    If you can afford the carbs, a breadstick or whole-grain roll are a nice indulgence. And if you’re feeling really ambitious, try my garlic knots (just be sure to plan ahead).

    Storage

    Once cooked, shrimp can be stored covered in the refrigerator for about 3 or 4 days.

    Just keep in mind that the crispy bread-crumb topping might get a bit soggy in the refrigerator. For that reason, I prefer to serve this dish right away.

    Other healthy shrimp recipes

    Shrimp is a great option for a lean, healthy protein that can be made with so many different flavors! Here are a few more healthy and delicious shrimp recipes that I know you’ll enjoy:

    When you’ve tried this dish, please don’t forget to let me know how you liked it and rate the recipe in the comments below!

    Recipe Card

    Shrimp Scampi in foil packets

    Shrimp Scampi Foil Packets (Oven or Grill)

    These shrimp scampi foil packets with artichoke hearts are healthy, flavorful, easy to cook, and a breeze to clean-up! Make them in the oven or on the grill for a quick and tasty meal.

    Prep Time:25 minutes

    Cook Time:15 minutes

    Total Time:40 minutes

    Author:Shelby Kinnaird

    Servings:4

    Instructions

    • Heat a small skillet over medium heat.

    • Add 1 teaspoon of olive oil and the panko breadcrumbs, then cook, stirring frequently, until the panko is golden brown, about 3 minutes.

    • Transfer the mixture to a small bowl. Stir in the lemon zest, Parmesan, and garlic, then set aside.

    • Tear off 4 large sheets of heavy-duty foil, about 18 inches long each.

    • Place 1/4 of the artichoke hearts in the middle of each sheet of foil. Season with salt to taste, then top each with a thyme sprig, 3 to 4 lemon slices, and 1 teaspoon of butter.

    • In a large bowl, toss the shrimp with the crushed red pepper and garlic.

    • Add 1/4 of the shrimp mixture on top of the artichoke mixture on each sheet of foil. Drizzle each with 1 tablespoon of white wine and a 1/2 tablespoon of olive oil.

    • Bring the opposite sides of foil together and fold at least twice to seal, leaving a little headroom for the air to circulate. Then, fold the open sides over at least twice.

    • Cook the packets either directly on an oven rack for 15 to 20 minutes at 400°F or on a hot grill for about 10 minutes. The shrimp should be opaque when done.

    • Open the packets carefully and top with the toasted panko breadcrumbs and fresh parsley.

    Recipe Notes

    This recipe is for 4 servings. Each serving is the contents of 1 foil packet. Leftovers can be stored covered in the refrigerator for 3-4 days. However, the breadcrumbs may become soggy, so I would recommend serving this dish right away.

    Nutrition Info Per Serving

    Nutrition Facts

    Shrimp Scampi Foil Packets (Oven or Grill)

    Amount Per Serving (1 packet)

    Calories 304 Calories from Fat 128

    % Daily Value*

    Fat 14.2g22%

    Saturated Fat 3.9g24%

    Trans Fat 0g

    Polyunsaturated Fat 4.2g

    Monounsaturated Fat 3.1g

    Cholesterol 14.6mg5%

    Sodium 867.6mg38%

    Potassium 51.8mg1%

    Carbohydrates 13.6g5%

    Fiber 2g8%

    Sugar 3.1g3%

    Protein 29.7g59%

    Vitamin A 550IU11%

    Vitamin C 22.3mg27%

    Calcium 80mg8%

    Iron 8.1mg45%

    Net carbs 11.6g

    * Percent Daily Values are based on a 2000 calorie diet.

    Course: Fish & Seafood

    Cuisine: Mediterranean

    Diet: Diabetic

    Keyword: shrimp foil packets, shrimp scampi, shrimp scampi foil packets



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    BBQ Turkey Burger – My Bizzy Kitchen

    By electricdiet / July 14, 2020


    My late husband and I loved to go out to eat, and on the weekends we would eat out at least twice if not three times.  The weekends were a slippery slope for me.  

    I would do great Monday through Friday and then come Friday night it’s as if I lost my mind and ate whatever I wanted, knowing that I “did good” the previous five days.  Well, that doesn’t work my friends.  Unless you want to gain and lose the same five pounds.

    I hit the reset button on June 13 when I weighed in at 190.2.  That’s the highest adult weight I’ve been in a very long time.  Not my all time high of 211 but I needed to focus and get my shit together.

    Guess what?  Just following the WW plan.  However, I do it a bit differently.  I am on Team Purple so I get 300 “free” foods to chose from and 16 points a week, plus an additional 35 weekly points, or a total of 147 points for the week.  Getting “blue dots” on the WW app means that you stayed within your point range for the day.

    Me?  I switch it up!  My points this past week from Saturday through Friday: 25, 17, 22, 18, 25, 26, 23 for a total of 156 points.  I lost 3 pounds this week.  I think it’s important to keep your body guessing about what it’s going to get, instead of eating exactly 5 points for breakfast, 5 points for lunch and 6 points for dinner.

    Hopefully that makes sense?!  My mantra this millionth time getting “back on track” is consistency, not perfection.  That’s it.  Oh, and it helped that I am nearly half way through my #dryjuly challenge!

    But let’s talk about turkey burgers!  I remember going out to Applebees with my late husband (he loved their 32 ounce $3 miller lite beers!) and I was bound and determined to eat healthy even as I was eyeing the three appetizer for dinner choice (um, fried zucchini, mozzarellas sticks and coconut shrimp – yes please!).

    I chose the turkey burger with sweet potato fries.  Go me!  It was delicious and I ate every bite. Until I got home and tracked the points and it was 33 points and 1250 calories and 40 grams of fat – what the what?!

    As my late husband used to say if something made him mad “turkey burgers were dead to me” and I didn’t make one for years.

    But now that ground turkey breast is zero points on my WW plan, I knew I had to give them another try.  My secret to a juicy turkey breast burger?  I Can’t Believe It’s Not Butter.

    It makes all the difference.  It seriously is the key to a juicy burger.  Another tip:  don’t flip the burger too soon.  Whether on the grill or in a cast iron skillet, let the burger cook to get that browned caramelized goodness.

    Print

    BBQ Turkey Burger

    The juiciest turkey breast burger you’ll ever make!  I am posting the recipe for one serving, so scale as needed.

    • Author: Biz
    • Prep Time: 5 minutes
    • Cook Time: 15 minutes
    • Total Time: 20
    • Yield: 1 1x

    Scale

    Ingredients

    • 4 ounces ground turkey breast
    • 1/4 teaspoon salt
    • 1/4 teaspoon pepper
    • 1 tablespoon favorite BBQ sauce (I used G. Hughes sugar free)
    • 2 tablespoons real bacon bits
    • 1 teaspoon I Can’t Believe It’s Not Butter Light
    • 14 grams favorite cheese
    • baby spinach or lettuce
    • 1 brioche bun (mine was 5 points and 160 calories)

    Instructions

    Mix all the ingredients from turkey breast to bacon bits. Divide burger into two patties. On top of one patty, spread the butter, top with the other half of the burger and, using your hands, squeeze the burger together, kind of pinching the sides so the butter doesn’t ooze out.

    Start in a skillet on medium low (or on a grill over low heat) for the first 6 minutes. Finish off over medium high heat on a stove for 2 minutes a side, or until a meat thermometer reaches 160 degrees. Let rest 5 minutes to let the residual heat finish cooking the burger to 165. Top with cheese at the last minute to melt.

    Notes

    Serve with your favorite sides – on #teampurle that would be zero point corn and potatoes for me!

    My whole dinner was 9 points, or 510 calories. #wortheveryone 😀

    Since the burger is basically zero points (but has calories!) go ahead and splurge on a good bun.  This was a perfect summer dinner last week.  

    So if you’ve been giving turkey burgers the stink eye for a while, give this one a try – pinky swear you’ll love it!

    Until next time, be well!

     





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    Diabetes & Sleep Apnea: Everything You Need to Know

    By electricdiet / July 12, 2020


    Sleep apnea is a far greater problem than it gets credit for — especially for people living with diabetes.

    Difficult to diagnose without proper overnight testing, too many people struggling to breathe properly during their sleep may not have any idea they aren’t getting enough oxygen every night.

    But sleep apnea can impact many aspects of your day-to-day life and overall health. And its link to diabetes is indisputable.

    In this article, we’ll discuss what sleep apnea is, common causes and symptoms, its relationship with type 1 and type 2 diabetes, and today’s best treatment options.

    Face of man sleeping with sleep apnea

    What is sleep apnea?

    Sleep apnea (also known as “obstructive sleep apnea” or “OSA”) is a condition defined by long pauses in breathing while you sleep. To qualify, the pause of breathing must be at least 10 seconds long, according to the National Sleep Foundation.

    The pause in breathing is the result of muscles of the back of your throat closing partially or failing entirely to stay open for varying periods of time while you sleep.

    The reason these pauses in breathing are worrisome and troublesome is that it can create a significant lack of oxygen in your blood which then leads to a variety of other problems.

    Consequences of untreated sleep apnea

    • Daytime exhaustion and fogginess
    • High blood pressure
    • Cardiac arrhythmia
    • Congestive heart failure
    • Heart attack
    • Stroke
    • Depression and mood issues
    • Memory issues
    • Insulin resistance
    • Increased risk of type 2 diabetes
    • Drowsy driving

    OSA can develop in children, too, although less common.

    Causes of sleep apnea

    While anyone could potentially develop sleep apnea, the following are characteristics or habits that increase your risk of developing the condition, according to Harvard:

    • Obesity: about 2/3s of people with OSA are overweight or obese
    • Family history of OSA or snoring
    • Abnormally smaller lower jaw or other abnormal facial characteristics
    • Recessed chin
    • Being male: far more people with OSA are male versus female
    • Smoking cigarettes
    • Large neck circumference
    • Large tonsils
    • Drinking alcohol before bedtime
    • Post-menopausal (for women)
    • Hypothyroidism (low levels of thyroid hormone)
    • Acromegaly (high levels of growth hormone)
    • Being over the age of 40 years old
    • Being African-American, Pacific-Islander, or Hispanic

    While there is another type of sleep apnea that results from your brain failing to manage normal breathing, that type is rare.

    The type most commonly experienced by the general population is obstructive sleep apnea and affects approximately 18 million people in the United States.

    Symptoms

    The signs and symptoms of sleep apnea are often easy to dismiss or easy to mistake as individual issues rather than many symptoms related to the same condition.

    The National Sleep Foundation lists the following as common signs and symptoms of sleep apnea:

    • Chronic snoring
    • Constantly feeling sleep-deprived
    • Difficulty concentrating
    • Depression
    • Irritability
    • Sexual dysfunction
    • Learning and memory difficulties
    • Falling asleep during normal daytime activities
      Disturbed sleep

    If you are a chronic snorer or suspect any of these symptoms may be regularly present in your life, talk to your primary care doctor about scheduling with a sleep specialist who can assess you for sleep apnea.

    Sleep apnea and diabetes: how are they related?

    Research has demonstrated over and over again that OSA and diabetes have an undeniable relationship, and are often found in the same patient.

    Let’s take a look at some of the most significant research.

    Sleep apnea increases blood sugar levels

    OSA has been found to increase oxidative stress, inflammation, neuroendocrine dysregulation, and alter glucose homeostasis, according to this 2016 study from the American Diabetes Association.

    The study’s finding urges healthcare professionals to assess every patient with type 2 diabetes for potential signs of sleep apnea, and vice versa — assessing patients with sleep apnea for high blood sugar levels.

    “Early recognition and interventions for OSA can be expected to improve insulin sensitivity and control of hyperglycemia in many patients. Clinicians must remain vigilant for signs and symptoms of OSA and monitor compliance with CPAP along with weight management, diet control, and medication adherence in patients with type 2 diabetes.”

    Sleep apnea linked to insulin resistance and type 2 diabetes

    This 2018 report on OSA evaluated dozens of studies on the condition and its implications and connections with other conditions.

    It was determined that patients with OSA had an increased risk of developing hypertension, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, dyslipidemia, and atherosclerosis.

    Sleep apnea increases your risk of type 2 diabetes

    This 2017 study from Taiwan determined that patients with OSA had a much higher likelihood of developing type 2 diabetes. In contrast, the study also determined that patients with type 2 diabetes did not necessarily have a higher likelihood of developing OSA.

    This simply means that OSA seems to be a precursor for developing type 2 diabetes, but type 2 diabetes is not a precursor to developing OSA in patients who have not already developed this sleep condition.

    A 2018 study from Japan echoed similar findings.

    “OSA patients are more likely than non-OSA populations to develop type 2 diabetes, while more than half of type 2 diabetes patients suffer from OSA.”

    Using a CPAP to treat OSA improves insulin resistance

    A CPAP device — which stands for “continuous positive airway pressure” — is the primary method of treatment for OSA, and this 2018 study from Japan found that consistent use of a CPAP improves a patient’s levels of insulin resistance.

    “CPAP improved glucose metabolism determined by the oral glucose tolerance test in OSA patients, and several studies have shown that CPAP improves insulin resistance, particularly in obese populations undergoing long-term CPAP.”

    This is significant in terms of treating a patient with both OSA and type 2 diabetes. By treating the OSA, the patient may see modest to moderate improvements in their blood sugar levels and overall diabetes health, too.

    Both type 2 diabetes and OSA increase risk of cardiovascular disease

    “As both diabetes and OSA lead to cardiovascular disease, clinicians and healthcare professionals should be aware of the association between diabetes and OSA,” explains the same 2018 study from Japan.  

    The study suggests that healthcare professionals should heavily consider treating patients with type 2 diabetes and/or OSA with a CPAP device to reduce the known stress both conditions have on a patient’s cardiovascular system.

    OSA increases the risk of STDR (sight-threatening diabetic retinopathy)

    This 2017 study from the United Kingdom found that patients with type 2 diabetes and existing diabetic retinopathy had a significantly increased risk of developing proliferative diabetic retinopathy, which is defined by the patient’s worsening vision.

    Using a CPAP device to treat the OSA resulted in a reduction of the progression of the STDR in these patients, but it was determined that further studies are needed to focus more intensely on the benefits of treating OSA to inadvertently treat STDR.

    Patients with type 1 diabetes have a higher risk of OSA

    “The prevalence of asymptomatic OSA is high in a cohort of patients with type 1 diabetes,” determined a 2017 study from Denmark.

    Other risk factors for the type 1 diabetes population included being older, overweight, and existing diagnosis of nephropathy (kidney disease).

    “OSA was present in 32 percent of the patients with normal BMI, in 60 percent of overweight patients, and in 61% of obese patients,” explains the study.

    Additionally, the study found that patients with type 1 diabetes and OSA showed very few symptoms, particularly very rarely reporting sleepiness compared to patients without OSA. This makes it harder to catch, diagnose, and treat.

    Healthcare professionals treating patients with type 1 diabetes should keep in mind that this population should be potentially screened for OSA if they are also over the age of 40, overweight, and have nephropathy.

    Treatment options

    If you think you may have sleep apnea, the first place to start seeking help is through your primary care doctor.

    Most likely, if you share your bed with a partner, it isn’t going to be news to you that you have a severely loud or disruptive snore. You might even want to try setting your phone up to record the sound of your own snore. This alone could reveal long gaps in breathing or very turbulent, inconsistent snore rhythms.

    Your doctor will then recommend you partake in a sleep study which means you’ll stay overnight at a “sleep center” to have your breathing monitored for an entire night.

    They will also monitor your eye movement, muscle activity, heart rate, respiratory effort, airflow, and the amount of oxygen in your blood.

    This will give your healthcare team a clear understanding of whether or not you have sleep apnea, and how severe your sleep apnea may be based on just how little oxygen your body is getting while you sleep.

    The number one treatment for sleep apnea, as mentioned earlier, is a CPAP device.

    A CPAP looks more uncomfortable than it really is, which can deter patients from pursuing getting treated in the first place.

    A CPAP is a mask that fits over your mouth and/or your nose, and it blows air into your airway to help keep it adequately open while you sleep.

    Research has found that it is by far the most effective treatment for sleep apnea, but one tricky aspect of this method is getting patients to use it consistently.

    The device itself also makes a light and soft noise when it’s turned on, which is similar to the sound of a noise machine. Ideally, the sound itself doesn’t interfere with your sleep and possibly improves your sleep by providing white noise.

    What else can you do to treat sleep apnea? Let’s take a look at all of the options recommended by the National Sleep Foundation:

    • Continuous positive airway pressure (CPAP) device: A mask that covers your mouth and/or nose and delivers air to help keep your airway open while you sleep
    • Oral Pressure Therapy (OPT): Similar to a CPAP device but without the mask, this treatment is a mouthpiece that delivers air to help keep your throat properly open while you sleep.
    • Expiratory Positive Airway Pressure (EPAP): This device covers your nostrils with a disposable adhesive valve that opens and ensures your airway stays open.
    • Dental appliances to reposition jaw and tongue
    • Upper airway surgery to remove excess tissue: If you have an anatomical facial abnormality, it could be corrected with surgery and enable your jaw and throat to stay open properly during your sleep.
    • Lose weight: Weight-loss can have a significant impact on sleep apnea. If you’re reluctant to use a device, let sleep apnea be the motivation you need to lose weight.
    • Avoid, reduce, or limit alcohol intake
    • Quit smoking
    • Sleep on your side instead of on your back

    While sleep apnea doesn’t sound terribly alarming at first, it can create a great deal of stress in the body and in your life if left untreated.

    This easy-to-miss condition can put your longterm health in danger. Don’t hesitate to get tested if suspect you may be struggling with sleep apnea.



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    Excitotoxicity and Overnutrition Additively Impair Metabolic Function and Identity of Pancreatic β-Cells

    By electricdiet / July 10, 2020


    Abstract

    A sustained increase in intracellular Ca2+ concentration (referred to hereafter as excitotoxicity), brought on by chronic metabolic stress, may contribute to pancreatic β-cell failure. To determine the additive effects of excitotoxicity and overnutrition on β-cell function and gene expression, we analyzed the impact of a high-fat diet (HFD) on Abcc8 knockout mice. Excitotoxicity caused β-cells to be more susceptible to HFD-induced impairment of glucose homeostasis, and these effects were mitigated by verapamil, a Ca2+ channel blocker. Excitotoxicity, overnutrition, and the combination of both stresses caused similar but distinct alterations in the β-cell transcriptome, including additive increases in genes associated with mitochondrial energy metabolism, fatty acid β-oxidation, and mitochondrial biogenesis and their key regulator Ppargc1a. Overnutrition worsened excitotoxicity-induced mitochondrial dysfunction, increasing metabolic inflexibility and mitochondrial damage. In addition, excitotoxicity and overnutrition, individually and together, impaired both β-cell function and identity by reducing expression of genes important for insulin secretion, cell polarity, cell junction, cilia, cytoskeleton, vesicular trafficking, and regulation of β-cell epigenetic and transcriptional program. Sex had an impact on all β-cell responses, with male animals exhibiting greater metabolic stress-induced impairments than females. Together, these findings indicate that a sustained increase in intracellular Ca2+, by altering mitochondrial function and impairing β-cell identity, augments overnutrition-induced β-cell failure.

    Introduction

    The loss of β-mass and function in response to metabolic stress is a major determinant of type 2 diabetes (T2D) (1). While multiple mechanisms, including glucolipotoxicity, excitotoxicity, inflammation, endoplasmic reticulum (ER) stress, and oxidative stress (25), have been implicated in metabolic stress–induced β-cell failure, the molecular and cellular mechanisms that actually cause the loss of β-cell function and development of T2D are not understood.

    Excitotoxicity refers to the pathological process in excitable cells in which overstimulation leads to a sustained increase in intracellular Ca2+ concentration ([Ca2+]i), resulting in disrupted homeostasis, loss of cell function, or cell death (6). In pancreatic β-cells, metabolic stress–induced increases in [Ca2+]i activate Ca2+/calmodulin-dependent kinases (CaMKs), calcineurin (a Ca2+-dependent phosphatase), and other Ca2+-dependent proteins, causing alterations in β-cell gene expression that negatively impact both β-cell mass and function (7). Increases in [Ca2+]i have been described in rat islets cultured in high glucose (8), in mouse islets from obese (db/db) mice (9), in islets of mice fed a high-fat diet (HFD) (10), and in β-cells that exhibit chronic membrane depolarization (11). Both the verapamil-induced blockage of Ca2+ influx (12) and genetic knockdown of Cavβ3, a Ca2+ channel subunit (13), by reducing [Ca2+]i, attenuate β-cell loss and diabetes in animal models, suggesting that an increase in [Ca2+]i is a fundamental determinant of stress-induced β-cell failure.

    Overnutrition, by elevating circulating free fatty acids (FFAs), contributes to insulin resistance, increasing insulin biosynthesis and secretion (14). The prolonged exposure of β-cells to FFAs elicits multiple responses, including the activation of ER stress, oxidative stress, and inflammatory signaling pathways (15,16). Most notably, FFA-induced oxidative stress triggers the release of Ca2+ from ER stores, increasing [Ca2+]i, accentuating ER stress, and inducing apoptosis (17).

    Sex also influences the response of β-cells to stress (18). Women are less likely than men to develop T2D and require a higher BMI to do so (19). Increased estrogen receptor signaling (20), sex-specific differences in islet DNA methylation status (21), and differences in the expression of islet-enriched transcription factors (TFs) and genes involved in cell cycle regulation (22) have all been suggested as causes for these differences.

    To obtain a systems-wide understanding of the effects of both excitotoxicity and overnutrition on β-cell function and gene expression, we used mice lacking Abcc8, a critical subunit of the ATP-dependent K+ channel (KATP). Previously, we have shown that β-cells from these mice exhibit chronic membrane depolarization and increases in [Ca2+]i that cause impairments in islet morphology, glucose tolerance, and β-cell identity (11,23). Because the loss of β-cell function in mice lacking Abcc8 develops slowly over several months (23), the individual and combined effects of excitotoxicity and overnutrition on β-cell function and gene expression were determined prior to the onset of hyperglycemia and glucotoxicity (11). Additionally, by using a recently described Ins2Apple allele, we avoided confounding effects of the MIP-GFP transgene (22).

    Research Design and Methods

    Mouse Lines and Husbandry

    The Abcc8tm1.1Mgn (23) and Ins2Apple (22) alleles were bred into and maintained as C57BL/6J congenic lines (stock 000664; The Jackson Laboratory). At weaning (3–4 weeks of age), mice were fed either regular chow (RC) (4.5% fat content) (5L0D; PicoLab) or HFD (60% fat content) (D12492; Research Diets, Inc.) for 5 weeks. Verapamil (1 mg/mL) (V4629; Sigma-Aldrich) was administered through the drinking water during the period of HFD feeding. All animal experimentation was performed under the oversight of the Vanderbilt University Institutional Animal Care and Use Committee.

    Glucose Homeostasis

    Intraperitoneal glucose tolerance tests (GTTs) were performed following a 16-h overnight fast. Blood glucose concentrations were measured at 0, 15, 30, 60, and 120 min after administering d-glucose (2 mg/g body mass). Insulin tolerance testing was performed following a 4-h morning fast by administering 0.1 units/mL insulin (in Dulbecco’s PBS) (Humulin R; Eli Lilly and Company) and measuring blood glucose concentrations at 0, 15, 30, 60, and 120 min.

    Islet Isolation and Culture

    Islets were isolated following injection of 0.6 mg/mL Collagenase P (Roche) into the pancreatic bile duct followed by Histopaque-1077 (Sigma-Aldrich) fractionation and handpicking. For FACS and RNA sequencing, islets from two to four mice were pooled for each sample. Islets were cultured in low-glucose DMEM (11966–025; Gibco) containing 1 g/L glucose and supplemented with 10% FBS and penicillin/streptomycin (100 mg/mL) (Gibco) at 37°C with 5% CO2 infusion and 95% humidity. Palmitic acid (PA) (P0500; Sigma-Aldrich) was diluted in 50% ethanol to 100 mmol/L and conjugated to an FA-free BSA (A6003; Sigma-Aldrich) to generate a 5 mmol/L PA/5% FA-free BSA stock solution. Experimental media concentrations of the compounds used were 100 μmol/L for tolbutamide (T0891; Sigma-Aldrich), 0.5 mmol/L for PA, and 50 μmol/L for verapamil (V4629; Sigma-Aldrich).

    β-Cell Isolation, RNA Isolation, and Quantitative PCR

    Purified β-cells were obtained as previously described (15) in which live cells expressing red fluorescence were sorted with a 100-μm nozzle using the FACSAria II instrument (BD Biosciences). Cells were collected in chilled Homogenization Solution from the Maxwell 16 LEV simplyRNA Tissue Kit (TM351; Promega), and RNA was isolated as directed. For quantitative PCR (qPCR), reverse transcription was done using a High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific). A total of 2 ng cDNA was used in real-time qPCR with Power SYBR Green PCR Master Mix (Thermo Fisher Scientific) using a CFX96 Real-Time PCR system (Bio-Rad Laboratories). Primers are listed in Supplementary Table 1.

    RNA Sequencing and Data Analysis

    RNA samples were analyzed using an Agilent 2100 Bioanalyzer, and only those samples with an RNA integrity number of seven or above were used. cDNA synthesis and amplification were performed using the SMART-Seq v4 Ultra Low Input RNA Kit for Sequencing (Takara Bio, Inc.) using 10 cycles of PCR. cDNA libraries were constructed using the Low Input Library Prep Kit (Takara Bio, Inc.). An Illumina NovaSeq 6000 instrument was used to produce paired-end, 150-nucleotide reads for each RNA sample. Paired-end sequencing of 31 samples produced ∼1.55 billion raw sequencing reads. The Spliced Transcripts Alignment to a Reference (STAR) application (16) was used to perform sequence alignments to the mm10 (GRCm38) mouse genome reference and GENCODE comprehensive gene annotations (release M17). Overall, 80–88% of the raw sequencing reads were uniquely mapped to genomic sites, resulting in 1.3 billion usable reads. HTSeq was used for counting reads mapped to genomic features (17), and DESeq2 was used for differential gene expression analysis (18). Padj <0.05 cutoff was used to define differentially expressed genes. Gene ontology (GO) analysis of differentially expressed genes was performed using Metascape (19).

    Mitochondrial Respirometry and mtDNA Copy Number

    Oxygen consumption rates (OCRs) of isolated islets were determined using a Seahorse XF96 respirometer (Agilent Technologies), as described (24). A total of 10–20 islets/well were loaded onto a Cell-Tak (Corning) precoated XF96 spheroid plate (Agilent Technologies) and preincubated for 2 h at 37°C without CO2 in a Seahorse assay DMEM (Agilent Technologies) supplemented with 3 mmol/L glucose, 1 mmol/L pyruvate, and 2 mmol/L glutamine. After measuring basal OCR, glucose (20 mmol/L), oligomycin (5 mmol/L), carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) (1 mmol/L), or antimycin A/rotenone (2.5 mmol/L) was added at indicated time points to modulate mitochondrial OCR response. For mtDNA copy number measurements, islet DNA was isolated with a DNeasy kit (Qiagen) and analyzed by qPCR with primers for mtDNA-encoded gene mt-CO1 and nuclear gene Ndufv1. Relative copy number was calculated as 2^([Ct(mtDNA) * E] − [Ct(nuclear DNA) * E]), where E is efficiency of corresponding qPCR determined from standard curves and Ct is threshold cycle.

    Results

    Excitotoxicity and Overnutrition Additively Impair Glucose Tolerance

    To compare the effects of excitotoxicity and overnutrition on pancreatic β-cells, we fed C57BL/6J (wild-type [WT]) and Abcc8 knockout (KO) mice either RC or HFD for 5 weeks. Both groups contained male and female animals (n = 7–8 of each sex), and all animals gained weight on HFD (Fig. 1A). Blood glucose measurements after 5 weeks showed that the KO animals had lower fasting blood glucose in comparison with WT mice (Fig. 1B), consistent with previous observations that Abcc8 KO mice have impaired glucagon secretion (25). In contrast, fed blood glucose levels were higher in the HFD-KO mice compared with the RC-KO and HFD-WT animals (Fig. 1C). Treatment with verapamil, a Ca2+ channel blocker, during HFD lowered the fed blood glucose concentration in both the HFD-KO and HFD-WT mice (Fig. 1C).

    Figure 1
    Figure 1

    Abcc8 KO mice exhibit impaired β-cell function after 5 weeks on HFD that is improved with the addition of verapamil. A: Weight gain on HFD for 5 weeks was similar for both WT and Abcc8 KO animals. Fasting (B) and fed (C) blood glucose measurements for RC- and HFD-fed mice at 8–9 weeks. KO mice have lower fasting blood glucose than WT mice. Fed blood glucose is elevated in HFD-KO and is lowered with the addition of verapamil (+ver). D: Intraperitoneal GTT results comparing RC- and HFD-fed mice at 8–9 weeks. HFD-KO mice have impaired glucose tolerance in comparison with WT and RC-KO mice. *P ≤ 0.05, **P ≤ 0.01: HFD-WT vs. HFD-KO; #P ≤ 0.05, ##P ≤ 0.01: HFD-KO vs. RC-KO. E: GTT results comparing HFD- and HFD+ver–fed mice at 8–9 weeks. n = 14–16. *P ≤ 0.05: HFD-WT vs. HFD-WT+ver; #P ≤ 0.05: HFD-KO vs. HFD-KO+ver. F: GTT area under the curve (AUC) measurements. Addition of verapamil improves glucose tolerance of HFD-WT and HFD-KO mice. n = 14–16 (7–8 males and 7–8 females) for each condition. Error bars: ± SEM. *P ≤ 0.05; **P ≤ 0.01; ****P ≤ 0.0001 (determined by ANOVA).

    After 5 weeks, HFD-KO mice exhibited greater glucose intolerance compared with the RC-KO, RC-WT, and HFD-WT mice (Fig. 1D and F). Verapamil treatment improved glucose tolerance in the HFD-WT mice, while in HFD-KO mice, the effect of the drug was apparent only at 120 min after glucose administration (Fig. 1E and F). Both the RC-KO and HFD-KO animals had increased insulin sensitivity compared with the RC-WT and HFD-WT mice, respectively (Supplementary Fig. 1A and C). However, while verapamil increased insulin sensitivity of HFD-WT compared with the RC-WT mice, it had no effect on the HFD-KO mice (Supplementary Fig. 1B and C). These findings indicate that Abcc8 KO mice are more insulin sensitive, have a higher fed blood glucose concentration, and are more intolerant of glucose on an HFD than are WT animals. Interestingly, coadministration of verapamil during HFD feeding normalized blood glucose concentration in the KO animals independent of improvements in insulin sensitivity. Together, these findings indicate that excitotoxicity increases the susceptibility of β-cells to the negative effects of overnutrition.

    Effects of Excitotoxicity and Overnutrition on β-Cell Gene Expression

    To determine how excitotoxicity, overnutrition, and both stresses affect gene expression, we performed RNA sequencing on FACS-purified β-cells. All mice were identical in strain (C57BL/6J) and age (8–9 weeks old), but differed by sex, the presence or absence of Abcc8, and diet (RC vs. HFD). Sample clustering by principal component analyses of data from 31 samples (Supplementary Table 2) showed clear separation of WT and KO samples and indicated that the effect of the Abcc8 KO was much greater than that of the HFD (Supplementary Fig. 2). After pooling the data from both sexes, we performed three differential expression (DE) analyses, as summarized in Supplementary Table 3.

    Excitotoxicity

    To determine effects of excitotoxicity, we first compared the RC-KO and RC-WT data sets. Similar to our previous report, which used an MIP-GFP transgene (11), we observed a profound alteration in the β-cell transcriptome with a total of 7,393 genes being affected (3,957 upregulated genes [URGs] and 3,436 downregulated genes [DRGs]) (Fig. 2A and B and Supplementary Table 4). The magnitude of gene dysregulation was similar to our prior study (R = 0.72) (Supplementary Fig. 3) with differences in dysregulated gene sets attributed to leaky growth hormone from the MIP-GFP transgene (22).

    Figure 2
    Figure 2

    β-Cell transcriptome changes in response to excitotoxicity in Abcc8 KO mice. A: Volcano plot showing distribution of differentially expressed genes (Log2FC over P value) in the RCKO vs. RC-WT RNA-sequencing comparison. Top 10 differentially expressed genes are indicated by names, and total numbers of URGs and DRGs are shown (Padj < 0.05). B: Distribution of dysregulated genes by biotype. C: Functional enrichment analysis of URGs and DRGs. Select top enriched pathways are shown. D: DE levels of select top URGs (top) and DRGs (bottom), with colors indicating gene functional associations. ECM, extracellular matrix; FDR, false discovery rate; Log2FC, log2 fold change of gene expression values in normalized counts in RC-KO vs. RC-WT comparison; TCA, tricarboxylic acid.

    GO term and pathway enrichment analysis of protein coding URGs and DRGs revealed that the URGs were enriched in mitochondrial genes involved in oxidative phosphorylation, mitochondrial organization, multiple metabolic pathways, and lysosomal genes (Fig. 2C and Supplementary Table 5). In contrast, DRGs were associated with microtubule cytoskeleton, insulin secretion, chromatin organization, transcription, FoxO and Mapk signaling, and cell junction organization. Several of the top URGs are critical for neural and β-cell development, including TFs (Ascl1, Fev, and Neurog3) and growth factors (Nog, Wif1, and Igf2) (Fig. 2D). Other top URGs include gastrin (Gast), a putative marker of dedifferentiating β-cells (26), the EF-hand domain Ca2+-binding protein S100a6, voltage-gated K+ channels (Kcnc2 and Kcns3), and Ca2+ channels (Slc24a33 and Cacng3), which are likely involved in compensatory regulation of ion flow in the absence of functional KATP channels (Fig. 2D). Top DRGs are involved in insulin secretion (Nnat and Ins1), cell junction formation (Cldn8 and Pcdh15), potassium ion transport (Trpm5 and Hcn1), response to vascular endothelial growth factor (Kdr and Flt1), and gene transcription (Npas4 and Egr4). These results indicate that β-cell excitotoxicity increases expression of many developmentally important TFs and genes required for mitochondrial energy production while also broadly downregulating genes involved in insulin secretion, chromatin maintenance, and cytoskeletal function.

    Overnutrition

    Next, we determined the effects of overnutrition on WT β-cells by comparing the HFD-WT and RC-WT data sets. This analysis revealed 2,372 affected genes (1,320 URGs and 1,052 DRGs) (Fig. 3A and B and Supplementary Table 4). Functional enrichment analysis indicated that URGs were involved in ER protein processing, ER stress, unfolded protein responses, glycan biosynthesis, and cell cycle regulation. In contrast, DRGs were involved in chromatin organization and response to hormone stimulus, as well as mammalian target of rapamycin signaling pathways (Fig. 3C and Supplementary Table 5). The top URGs included hormone receptors (Ptger3 and Oxtr), immune cell surface proteins (Cd74 and H2-Eb2), and cell cycle regulators (Cdc20 and Ccnb1) (Fig. 3D). Top DRGs included receptors (Erbb2 and Hspg2), extracellular matrix proteins (Olfm2 and Hspg2), secreted growth factors (Igfbp5 and Angptl7), and TFs (Trnp1 and Epas1). These results indicate that overnutrition causes increased expression of genes involved in ER protein processing and β-cell proliferation and downregulation of genes involved in mammalian target of rapamycin signaling and chromatin maintenance.

    Figure 3
    Figure 3

    β-Cell transcriptome changes in response to overnutrition (HFD) in WT mice. A: Volcano plot showing distribution of differentially expressed genes (Log2FC over P value) in HFD-WT vs. RC-WT RNA-sequencing comparison. Top 10 differentially expressed genes are indicated by names, and total numbers of URGs and DRGs are provided (Padj < 0.05). B: Distribution of dysregulated genes by biotype. C: Functional enrichment analysis of URGs and DRGs. Select top enriched pathways are shown. D: DE levels of select top URGs (top) and DRGs (bottom), with colors indicating gene functional associations. ECM, extracellular matrix; ERAD, ER-associated protein degradation; FDR, false discovery rate; Log2FC, log2 fold change of normalized gene expression between HFD-WT and RC-WT samples; mTOR, mammalian target of rapamycin.

    Excitotoxicity and Overnutrition

    To determine the combined effects of excitotoxicity and overnutrition, we compared the HFD-KO and RC-WT data sets and identified 8,836 dysregulated genes (4,322 URGs and 4,514 DRGs) (Fig. 4A and B and Supplementary Table 4). URGs were involved in oxidative phosphorylation, the citric acid cycle, and nucleotide metabolism, whereas DRGs were involved in cytoskeleton, insulin secretion, cell projection and cell junction organization, and chromatin and transcriptional regulation (Fig. 4C and Supplementary Table 5). Many of the top URGs were also increased in the RC-KO (Ascl1 and Stc2) and HFD-WT (Cd74 and Cdc20) mice (Fig. 4D). Interestingly, genes involved in lipid uptake (Fabp3 and Apoe), stimulation of ketogenesis, and impairment of glycolysis (Hmgcs2 and Pdk4) were only upregulated in response to the combined stresses. The top DRGs included genes involved in cell adhesion (Gjd4 and Dlagap2), acid transporters (Slc28a2 and Slc7a11), and many genes that were also downregulated in either RC-KO (Npy and Nnat) or HFD-WT (Igfpb5 and Atf5) mice. These findings indicate that the combination of excitotoxicity and overnutrition causes a further increase in the expression of β-cell genes involved in energy metabolism and ATP production, as well as genes linked to a decrease in glucose and an increase in FA-derived ketone utilization as an energy source. At the same time, genes associated with cytoskeleton and cell junction organization are downregulated.

    Figure 4
    Figure 4

    β-Cell transcriptome changes in response to excitotoxicity and overnutrition (HFD) in Abcc8 KO mice. A: Volcano plot showing distribution of differentially expressed genes (Log2FC over P value) in HFD-KO vs. RC-WT RNA-sequencing comparison. Top 10 differentially expressed genes are indicated by names, and total numbers of URGs and DRGs are provided (Padj < 0.05). B: Distribution of dysregulated genes by biotype. C: Functional enrichment analysis of URGs and DRGs. Select top enriched pathways are shown. D: DE of select top URGs (top) and DRGs (bottom). Colors indicate gene functional associations. FDR, false discovery rate; Log2FC, log2 fold change HFD-KO vs. RC-WT; TCA, tricarboxylic acid.

    Excitotoxicity and Overnutrition Affects Many of the Same Genes and Pathways

    To better categorize the many different transcriptional responses, we performed a meta-analysis of genes dysregulated in three comparisons (Fig. 5A). Major functional categories shared among URGs included oxidative phosphorylation, mitochondrial organization, metabolic pathways, and oxidative stress response, and shared downregulated pathways were chromatin organization, cytoskeleton and cell organization, and DNA damage response (Fig. 5B and C). The large overlap in genes dysregulated in response to both excitotoxicity and overnutrition (Fig. 6A) suggests that Ca2+-mediated nuclear responses are involved in many of the responses of β-cells to overnutrition. Of the 620 URGs that were similarly affected by excitotoxicity (RC-KO vs. RC-WT), overnutrition (HFD-WT vs. RC-WT), or excitotoxicity and overnutrition (HFD-KO vs. RC-WT), the most highly affected genes were Mc5r, a melanocortin receptor, Aldh1a3, an oxidoreductase for which expression correlates with β-cell failure (27), and Gabra4, a GABA receptor subunit that potentiates insulin secretion (28). In contrast, 522 DRGs were shared among all three comparisons with Trnp1, a regulator of cell cycle progression (29), tribbles pseudokinase 3 (Trib3), a multifunctional signaling protein involved in coordinating stress-adaptive metabolic responses (30), and glucagon receptor (Gcgr) being the most highly downregulated.

    Figure 5
    Figure 5

    GO terms and pathways common for β-cell genes dysregulated in excitotoxicity, overnutrition, and the combination of both stresses. A: Cord diagrams show genes (purple curves) and GO terms/pathways (blue curves) shared among lists of URGs and DRGs from three comparisons. Excitotoxicity (blue, RC-KO vs. RC-WT comparison), overnutrition (green, HFD-WT vs. RC-WT comparison), and excitotoxicity and overnutrition (green, HFD-KO vs. RC-WT comparison). Enrichment network visualization of GO terms/pathways shared among URGs (B) and DRGs (C) from the three comparisons. Node size is proportional to the number of genes in GO category, with pie charts indicating a proportion of genes from each comparison. Intensity of a node border color indicates GO category enrichment P value (from 10−48 to 10−2). AA, amino acid; TCA, tricarboxylic acid.

    Figure 6
    Figure 6

    Overlapping β-cell genes dysregulated in excitotoxicity, overnutrition, and the combination of both stresses. A: Venn diagrams indicating overlap between DRGs or DRGs (Padj < 0.05) identified from each pairwise comparison, with select top dysregulated genes indicated for each overlap. Excitotoxicity (blue, RC-KO vs. RC-WT comparison), overnutrition (light green, HFD-WT vs. RC-WT comparison), and excitotoxicity and overnutrition (pink, HFD-KO vs. RC-WT comparison). Genes in the circle that overlap among all three comparisons are overlapping stress URGs or DRGs. B: Functional enrichment analysis of URGs and DRGs. Select top enriched pathways are shown. ERAD, ER-associated protein degradation; TCA, tricarboxylic acid.

    Functional gene enrichment analysis showed that overlapping stress URGs are involved in ER protein processing, glycan biosynthesis, metabolic pathways, oxidative phosphorylation, and lysosomes (Fig. 6B and Supplementary Table 5). Included were genes involved in carbohydrate metabolism (Me3 and Mdh1), amino acid metabolism (Gatm and Oat), FA β-oxidation (Acad11 and Acadvl), components of complexes I–V of mitochondrial electron transport chain (Uqcrfs1, Atp5d, Cox6b1, and Ndufc2), and mitochondrial rRNA proteins (Mrps12 andMrpl51) (Supplementary Fig. 4). Common URGs also include oxidoreductases (Ald1a3 and Aass), secreted proteins (Gc and Vgf), redox homeostasis maintenance genes (Gsto2 and Gpx3), lysosome (Ctsh and Dapl1), ER protein folding (Ppib and Selenos), and vesicle traffic (Rgs8) genes. Notably, genes involved in Ca2+ signaling (Camk1d and Mapkapk3) and TFs that are activated by Ca2+ signaling (Mef1c and Nfatc1) are among common URGs (Supplementary Fig. 4). Other upregulated TFs include Fev, Bach2, Etv1, Ppargc1a, and Bhlha15. Overlapping stress-induced URGs also contain genes involved in DNA damage cell-cycle checkpoint (Check1 and Ccng1), apoptosis regulation (Bcl2 and Endog), potassium ion transport (Kcnk13 and Slc12a2), receptors (Gabra4 and Gfra4), extracellular matrix (Col8a2 and P3h2), and immune response (H2-Eb1 and Tnfrsf11b).

    DRGs common to all three comparisons are involved in transcription, chromatin modification, protein phosphorylation, as well as adherens junctions and FoxO1 signaling pathways (Fig. 6B and Supplementary Table 5). Downregulated TFs included known regulators of β-cell identity and function (Myt1, Thra, Myt1l, and Stat5a) and many for which the role in β-cells has not been studied (Mesp2, Phf21b, Otub2, and Chd7) (Supplementary Fig. 5). Over 40 proteins involved in epigenetic regulation were decreased, including chromatin-modifying enzymes (Kdm6b, Jmjd1c, and Kat2b), DNA methylation enzymes (Dnmt3a and Tet3), and miRNA-processing proteins (Ago1 and Tnrc6c). Common DRGs also included those involved in regulation of circadian rhythms (Prkab, Prkag2, and Nr1d1), the DNA damage response (Plk3, Taok1, and Primpol), Bmp and Wnt signaling (Acvr1c, Bmpr2, and Amer1/2), cell junction and polarity (Nectin1, Cldn4, Dlgap3, and Pard3), and cilia morphogenesis (Alms1, Cep162, Rfx3, and Ulk4) (Supplementary Fig. 5). In addition, common DRGs were for receptors (Ffar1 and Trpc1), kinases (Prkab2 and Jak), the phosphatidylinositol 3-kinase/AKT/FoxO1 signaling pathway (Akt3, Insr, and Foxo1), Ca2+ transport (Trpc1 and Grin2c), and proteins involved in amino acid transport (Slc7a11 and Slc36a1). A total of 114 long noncoding RNAs (lncRNAs) were also reduced in all three comparisons (Supplementary Fig. 6).

    Analysis of genes that were dysregulated only in the presence of both stresses (1,098 URGs and 1,407 DRGs) (Fig. 6A) showed a further increase in oxidative phosphorylation, translation, and nucleotide metabolism genes and a decrease in microtubule-based processes, RNA transport, cilia, and nuclear pore organization genes (Supplementary Fig. 7 and Supplementary Table 5). Importantly, an increase in genes that impair glucose utilization for energy production (Hmgcs2 and Pdk4) was observed only when excitotoxicity and overnutrition were combined, suggesting that the two stresses additively cause metabolic inflexibility.

    Sex Influences the Responses to Excitotoxicity and Overnutrition

    To determine how sex affects the response of β-cells to excitotoxicity and overnutrition, we reanalyzed our glucose homeostasis measurements and transcriptome data to extract these differences. As shown in Supplementary Figs. 8 and 9, male WT and KO mice gained more weight and had higher fed glucose concentrations and greater glucose intolerance than females of the same genotypes after 5 weeks on HFD. Verapamil treatment during HFD improved glucose tolerance in both the WT and KO males, but not in females of the same genotypes (Supplementary Fig. 9). However, while verapamil improved insulin tolerance in both the WT males and females, it had no effect on the KO mice (Supplementary Fig. 10). These findings indicate that male mice are more susceptible to negative effects of increased [Ca2+]i than are female animals.

    To determine how sex affects β-cell stress responses, we performed four different female-versus-male pairwise comparisons on the RNA-sequencing data sets (Supplementary Tables 3 and 4). Comparison of the RC-WT, RC-KO, and HFD-KO data sets in this manner yielded 140, 36, and 126 sex-specific genes, respectively (Padj < 0.05) (Supplementary Table 3). The lower number of sex-specific changes in the RC-KO and HFD-KO mice, compared with the RC-WT mice, suggests that the marked perturbation of the β-cell transcriptome that occurs in Abcc8 KO mice hinders the detection of sex-related differences. However, 2,618 were differentially expressed between female and male HFD-WT data sets. Overlaying all of the differentially expressed genes from the four pairwise comparisons revealed seven core sex-enriched genes, with Xist, Fmo1, and Kdm6a being female enriched and Kdm5d, Uty, Eif2s3y, and Ddx3y being male enriched (Supplementary Fig. 11A).

    GO analysis of sex-enriched genes from HFD-WT comparison revealed that female-enriched pathways included oxidative phosphorylation, proteasome degradation, spliceosome, glutathione metabolism, and adrenergic signaling. Male-enriched pathways included ER to Golgi vesicle traffic, autophagy, and cell cycle (Supplementary Fig. 11B and Supplementary Table 5). Among the top genes expressed higher in females on HFD were neuropeptides (Npy and Pyy), hormones (Gcg and Sst), as well as developmental endocrine TFs (Neurog3, Mafb, Fev, Arx, and Hhex) (Supplementary Fig. 11C). In males, the more abundantly expressed genes included Mc5r and Aldh1a3, cell proliferation genes (Mki76 and Ccna), DNA damage-response genes (Pole and Fanca), and transcriptional regulators (Chd5, Bach2, and Txnip). Overall, transcriptional response of male β-cells to HFD indicates a greater increase in β-cell proliferation, secretory function, autophagy, and associated DNA repair and ER-associated protein degradation pathways. The transcriptional response of female β-cells to HFD shows an increase in mitochondrial function, glutathione antioxidant defense, adrenergic signaling, and changes in β-cell identity.

    Dysregulated Transcription Factor Gene Expression Is Modulated by Increased [Ca2+]i and PA In Vitro

    Because our in vivo analyses revealed the modulation of genes involved in mitochondrial energy production and the maintenance of β-cell identity, we further analyzed Ppargc1a, Bach2, Thra, and Myt1 in cultured islets by RT-PCR (Fig. 7A). Ppargc1a is a transcriptional coregulator that is central to activation of mitochondrial energy metabolism, FA β-oxidation, and mitochondrial biogenesis (31). Bach2 belongs to a family of TFs induced by oxidative stress that may play a role in immune-mediated β-cell apoptosis (32). Myt1 and Thra, a thyroid hormone nuclear receptor, both contribute to the function of mature β-cells (33,34). Cultured WT mouse islets were treated with tolbutamide, a KATP channel inhibitor, PA, or a combination of both agents alone and with verapamil. After 24 h, the expression of Ppargc1a and Bach2 was increased, and Thra and Myt1 decreased, in response to tolbutamide alone. These changes were greatly accentuated when tolbutamide and PA were combined (Fig. 7B) and largely negated with the addition of verapamil. While the effect of PA by itself was generally small, its combination with tolbutamide was strongly additive, particularly for Ppargc1a. These findings provide additional evidence for rapid changes in key β-cell TFs and FA signaling in response to a rise in [Ca2+]i.

    Figure 7
    Figure 7

    Expression of overlapping stress-dysregulated TFs is modulated by increased [Ca2+]i and PA in vitro. A: Heat map of expression of TF genes Ppargc1a, Bach2, Thra, and Myt1 in β-cells from RC-WT, HFD-WT, RC-KO, and HFD-KO mice. RNA-sequencing data were normalized across all data sets, with color intensity indicating relative gene expression level within each row. B: RT-qPCR results using whole-islet RNA from WT islets treated for 24 h with 100 μmol/L tolbutamide (Tol), 0.5 mmol/L PA, a combination of both (Tol+PA), and with 50 μmol/L verapamil (Tol+PA+Ver). Expression of Ppargc1a and Bach2 is upregulated and expression of Thra and Myt1 is downregulated in response to drug treatment, with the most pronounced effect occurring in response to PA. The effects are negated when Ca2+ influx is blocked with verapamil. Data from five experiments containing both male and female samples were averaged for a total of 10 different islet samples. Error bars: ± SEM. **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001 (determined by ANOVA). Cont, control; max, maximum; min, minimum.

    Excitotoxicity and Overnutrition Additively Impair Mitochondrial Function

    In β-cells, mitochondrial metabolism is essential for coupling glucose metabolism to insulin secretion. To determine whether the observed increases in genes involved in mitochondrial respiration, organization, and FA β‐oxidation reflect actual changes in mitochondrial function, we compared mitochondrial OCR and mitochondrial biogenesis of RC-WT, RC-KO, HFD-WT, and HFD-KO islets. OCR measurements (Fig. 8A) showed that basal respiration rate reflecting the cell baseline metabolic energy production was progressively increased in HFD-WT, RC-KO, and HFD-KO islets (Fig. 8B). Similarly, metabolically stressed islets also had increased spare respiratory capacity, indicating increased ability to respond to increased energy demand (Fig. 8C) and increased mtDNA copy number (Fig. 8F). These results are consistent with corresponding increases in both mitochondrial respiration and biogenesis gene expression. However, the change in OCR in response to glucose is significantly decreased in RC-KO islets and almost completely ablated in HFD-KO islets (Fig. 8D), indicating that excitotoxicity and overnutrition additively impair mitochondrial glucose metabolism, most likely due to an increased FA β-oxidation, a rise in metabolic inflexibility, and mitochondrial damage. Consistent with an additive increase in mitochondrial damage, mitochondrial coupling efficiency is decreased and proton leak is increased in HFD-KO islets (Fig. 8E and F). These findings directly indicate that excitotoxicity and overnutrition additively impair mitochondrial glucose metabolic coupling function.

    Figure 8
    Figure 8

    Excitotoxicity and overnutrition affect islet mitochondrial function. A: OCR profiles measured by Agilent Seahorse mitochondrial stress assay. Islets from RC-WT, HFD-WT, RC-KO, and HFD-KO male mice at 8–9 weeks of age were consecutively treated with 20 mmol/L glucose (20G), 5 mmol/L oligomycin A (Oligo), 1 mmol/L FCCP, and 2.5 mmol/L antimycin A/rotenone (AA/Rot). n = 12 wells for each condition. *P ≤ 0.05, RC-WT vs. HFD-KO; #P ≤ 0.05, RC-KO vs. HFD-WT. B: Basal respiration was increased in HFD-WT, RC-KO, and HFD-KO islets. Basal respiration rate was calculated by subtraction of nonmitochondrial respiration from basal respiration rate. C: Spare respiratory capacity, or the ratio of basal respiration to maximal respiration after FCCP injection (×100), was increased in RC-KO islets. D: Glucose-stimulated OCR response was decreased in RC-KO and HFD-KO islets. Glucose response was calculated by subtracting basal respiration rate from the OCR after glucose injection. E: Coupling efficiency, or the ratio of basal respiration to ATP production rate (×100), was decreased in HFD-KO islets. The ATP production rate was calculated by subtracting the minimal rate after oligomycin injection from the basal respiration rate. F: Proton leak, or the minimal rate after oligomycin injection minus nonmitochondrial respiration, was increased in RC-KO and HFD-KO islets. G: Relative mtDNA copy number was increased in HFD-WT, RC-KO, and HFD-KO islets. mtDNA to nuclear DNA (nDNA) using real-time PCR. Error bars: ± SEM. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001 (determined by ANOVA).

    Discussion

    To gain a systems-wide understanding of pancreatic β-cell failure, we explored the additive effects of excitotoxicity and overnutrition on β-cell function and gene expression. Among the many changes that occur in β-cells in response to metabolic stress, we identified several critical alterations that may be tipping points for the development of T2D.

    Excitotoxicity and HFD Additively Impair β-Cell Function

    It has long been known that C57BL/6J (WT) mice develop insulin resistance and impaired β-cell function on an HFD (35). Our studies strongly suggest that an increase in [Ca2+]i, as occurs in the Abcc8 KO β-cells, increases the propensity of β-cell to fail in response to HFD and, conversely, verapamil, which blocks calcium entry and protects against the loss of β-cell function. RC-KO mice, which are euglycemic at 8–9 weeks of age (11,23), exhibit greater insulin sensitivity than RC-WT mice, as has been reported for mice lacking Kcnj11, another essential KATP channel component (36). While HFD predictably caused insulin resistance in WT mice, Abcc8 KO mice, like Kcnj11 KO animals (37), remained insulin sensitive on HFD, indicating that observed impairments in glucose homeostasis are mostly due to loss of β-cell function. Furthermore, while verapamil had no effect on insulin sensitivity in the KO mice, it increased the insulin sensitivity of WT mice on an HFD. Thus, our results not only confirm that Ca2+ channel blockers attenuate the development of obesity-induced insulin resistance (38), but they also indicate that the protective effects of these agents extend to β-cells. Moreover, they also indicate that an increase in [Ca2+]i, besides contributing to obesity-induced insulin resistance (39), has a negative effect on β-cell function. Indeed, given the pleiotropic metabolic effects of dysregulated Ca2+ homeostasis, it is noteworthy that the effects of Ca2+ channel blockers in both type 1 diabetes and T2D are now being investigated (40,41).

    β-Cell Transcriptome Changes in Response to Excitotoxicity, HFD, and a Combination of Both Stresses

    Excitotoxicity and overnutrition each have a major impact on β-cell gene expression, and together, the two stresses affect the expression of 11,952 unique genes, or nearly three-quarters (72%) of all genes expressed in β-cells. We also observed an overlap between genes and pathways that were dysregulated in response to both stresses, suggesting that increased [Ca2+]i may be involved in mediating the nuclear responses of other metabolic stresses.

    Energy Metabolism and Mitochondrial Function

    The largest category of genes upregulated by excitotoxicity and/or overnutrition are those involved in mitochondrial function, metabolism, and oxidative phosphorylation. Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells, and mitochondrial dysfunction plays a key role in development of T2D (42). Increased [Ca2+]i, in both normal and pathological states, invariably leads to increased mitochondrial Ca2+ uptake that stimulates mitochondrial Ca2+-sensitive metabolic enzymes and oxidative phosphorylation in the electron transport chain (43). However, a persistent increase in mitochondrial [Ca2+] and respiration may lead to an increase in reactive oxygen species production, collapse of the mitochondrial membrane potential, and mitochondrial dysfunction (6). Consistently, we observed that even though mitochondrial biogenesis and basal respiration are increased in KO islets, they also exhibit decreased coupling efficiency and increased proton leak upon addition of HFD, indicating mounting mitochondrial damage. Normally, damaged mitochondria are replaced by the combination of mitophagy, a lysosomal-based degradation process, and the production of new mitochondria that occurs through mitochondrial biogenesis. A balance between these processes is essential for normal β-cell function (44). Excitotoxicity increases the expression of multiple mitochondrial and lysosomal genes, as well as master regulators of both mitochondrial (Ppargc1a) and lysosomal (Tfeb) biogeneses, potentially maintaining biogenesis/mitophagy balance. However, the combination of both excitotoxicity and overnutrition shifts this balance, as there is a further increase in mitochondrial energy metabolism, oxidative stress, and DNA damage-response genes, indicating an increase in reactive oxygen species and mitochondrial damage, while expression of lysosomal genes is not further changed, and several mitophagy-associated genes, such as Clec16a and Prkn (45), become downregulated. These results suggest that the combination of excitotoxicity and overnutrition overwhelms the ability of β-cells to replace metabolically damaged mitochondria.

    Ppargc1a, a central transcriptional regulator of mitochondrial biogenesis, energy metabolism, and FA β-oxidation, is also increased in β-cells in response to both excitotoxicity and overnutrition. PPARGC1A interacts with multiple TFs and chromatin modifiers to regulate metabolic reprogramming in response to diet and oxidative stress and is implicated in pathogenesis of T2D (46). Ppargc1a is necessary for normal β-cell function (47), and its overexpression causes β-cell dysfunction (48). In this study, we show that expression of Ppargc1a is induced in cultured WT islets in response to increases in [Ca2+]i and is further increased with the addition of PA. This finding further implicates [Ca2+ ]i as an important regulator of mitochondrial metabolism in β-cells and suggests that an increase in [Ca2+]i causes the rapid upregulation of Ppargc1a, most likely through the activation of Ca2+-dependent CaN/CaMK/MAPK/AMPK signaling pathways. Similar signaling pathways are activated in skeletal muscle cells in response to exercise (49). In support of this hypothesis, excitotoxicity and overnutrition both upregulate Mef2c, a known target of Ca2+ signaling and a known activator of Paprgc1a in muscle, several CaMK and MAPKs, and multiple Ppargc1a target genes (Supplementary Fig. 12A). Similar to the activation of Ppargc1a, we also confirm an additive effect of increased [Ca2+]i and PA on the upregulation of Bach2, an oxidative stress–responsive TF, and the downregulation of both Myt1 and Thra, two other TFs important for the function of mature β-cells. However, less is known about how these other important genes are regulated and how they may contribute to normal β-cell function and the maintenance of β-cell identity.

    Coupling of glucose metabolism to insulin secretion is an important aspect of mitochondrial function in β-cells. We find that the combination of excitotoxicity and overnutrition increases expression of genes that contribute to metabolic inflexibility or the decreased ability to use glucose as an energy source, another key feature of β-cell failure (50). Similar to overnutrition alone, excitotoxicity alone causes an increase in genes involved in FA β-oxidation, indicating that β-cells partially switch to utilization of fat as a fuel in response to an increased [Ca2+]i, a process known as glucose sparing (Supplementary Fig. 12B). This switch is reflected in reduced ability of KO islets to increase mitochondrial respiration in response to glucose. However, in addition to FA β-oxidation, combination of excitotoxicity and overnutrition causes increases in Pdk4, a kinase that inhibits pyruvate flux into the tricarboxylic acid cycle, promoting FA and ketone body utilization (51), and Hmgcs2, a rate-limiting enzyme in ketone body production that is activated by FAs (52). Because these changes would be expected to impair glycolytic flux and cause metabolic inflexibility (Supplementary Fig. 12C), they may explain the observed collapse of mitochondrial glucose response in HFD-KO islets. Therefore, our data suggest a tipping point at which the combination of an increase in [Ca2+]i and an elevation in FAs causes the β-cell to cease relying on glycolysis and to switch to FAs and ketones as their fuel source, impairing their ability to sense and respond to changes in the blood glucose concentration.

    ER Protein Folding and Protein Glycosylation

    Glycosylation is a process during which glycans (mono- or oligosaccharides) are attached to proteins in the ER and Golgi that serve as a quality control signal in ER protein folding (53). In β-cells, increases in protein glycosylation cause ER stress, eventually leading to apoptosis (54). We found that overnutrition in particular increased expression of genes associated with ER protein folding and N– and O-linked protein glycosylation, suggesting that the stability, localization, trafficking, and function of many receptors, ion channels, nutrient transporters, and TFs are also adversely affected, likely contributing to development of T2D (55).

    β-Cell Structure: Cytoskeleton, Cell Polarity, and Cell Adhesion

    Excitotoxicity, overnutrition, and the combination of both stresses downregulate genes important for cell organization and secretory function of β-cells, including cell adhesion, cell junctions, cilia, cytoskeleton, and vesicular trafficking genes. We have previously identified impairments in islet architecture of Abcc8 KO mice (11), suggesting that critical cell-to-cell contacts, which are necessary for insulin secretion, may become impaired (56). The downregulation of synaptic vesicle-targeting proteins, GTPases, and cytoskeletal proteins has been shown to affect insulin exocytosis (57). Similarly, alterations in β-cell polarity may occur as genes associated with the apical domain (Pard3) and associated primary cilia (Alms1 and Cep162) and lateral domain (Dlgap3 and Nectin1) are downregulated, and genes associated with the vasculature-facing basal domain (Col8a2, Ntn4, and Ppfia3) are increased (58). These changes indicate that Ca2+ signaling in β-cells is crucial for maintaining cell polarity and cytoskeleton dynamics and that a chronic increase in [Ca2+]i impairs the ability of these cells to secrete insulin.

    β-Cell Identity

    Another important category of genes downregulated in metabolically stressed β-cells is those involved in transcriptional control. Besides decreases in many TFs that are necessary for function of mature β-cells (Myt1, Thra, Pbx1, Stat5a, and Nrf1), we also identified several other stress-inhibited TFs (Mesp2, Klf7, Nfia, Ikzf3, and Chd7) that may be critical for maintaining β-cell identity and function. Similarly, many chromatin modifiers, including histone methyltransferases and acetyltransferases, were downregulated in response to both stresses. Among these is Dnmt3a, a DNA methyltransferase important for silencing of developmental or “disallowed” metabolic genes in mature β-cells (59). Consistent with this, several disallowed genes (60) (Slc16a, Oat, and Aldob) are upregulated in response to excitotoxicity and/or overnutrition. Finally, maintenance of the epigenetic and transcriptional landscape of β-cells is also regulated by lncRNAs (61), and we identified multiple lncRNAs that are downregulated in response to these two metabolic stresses.

    Effects of Sex on β-Cell Stress Responses

    Male rodents have a greater propensity for β-cell failure than do females (18). In this study, we analyzed the effects of excitotoxicity and/or HFD on β-cell function and gene expression in both sexes. We found that female animals (both WT and Abcc8 KOs) withstand overnutrition better than males. These results are consistent with previous data on HFD-WT mice (62) and may reflect the protective influence of female sex hormones on β-cell function and metabolism (63). Interestingly, verapamil improved insulin sensitivity and glucose clearance in both the HFD-WT and HFD-KO males, but had little effect in females, suggesting that males are more negatively affected by a stress-induced increase in [Ca2+]i than females. Testosterone is known to increase [Ca2+]i in multiple tissues (64) and may also predispose β-cells for dysfunction associated with further [Ca2+]i increase due to increased metabolic load.

    Analysis of sex differences on a transcriptome level in WT mice confirmed our previous findings that female β-cells express higher amounts of several TFs important for β-cell function including Mlxipl, Nkx2-2, and Hnf1b (22). Interestingly, we were only able to detect a few sex-related changes in β-cells from both RC- and HFD-Abcc8 KO mice, suggesting that the massive gene expression changes that occur in the Abcc8 KO mice may mask the detection of sex-related differences. However, overlaying the differentially expressed genes from all four female to male transcriptome comparisons allowed us to identify three core female-enriched β-cell genes (Xist, Fmo1, and Kdm6a) and four male-enriched genes (Kdm5d, Uty, Eif2s3y, and Ddx3y). All of the male-enriched genes are located on the Y chromosome, whereas only two of the female-enriched genes (Xist and Kdm6a) are located on the X chromosome. Kdm6a, Uty, and Kdm5d all code for histone demethylases that may be involved in sex-specific epigenetic regulation of gene expression (65,66). Our discovery that Fmo1, an autosome-located gene, is enriched in female β-cells is interesting, as this gene encodes a flavin-containing monooyxgenase 1, a drug-metabolizing enzyme that regulates energy balance (67). Another member of the same family, Fmo4, was also upregulated in females on HFD. Overall, the most profound sex differences revealed by our analysis were in the β-cell transcriptome on HFD (2,618 genes). Female β-cells express higher levels of genes involved in oxidative phosphorylation, suggesting they may have higher energy metabolism than do male β-cells. Genes involved in prevention of oxidative damage, such as glutathione peroxidases, are also higher in female cells, suggesting a mechanism enabling female β-cells to tolerate overnutrition better than males. Female β-cells also express more of neuropeptides Npy and Pyy, both of which could be protective against β-cell damage (68,69), and the adrenergic receptor Adrb2, signaling through which can increase insulin secretion. Consistent with this, it was recently reported that pancreas-specific loss of Adrb2 causes glucose intolerance and impaired glucose-stimulated insulin secretion only in female mice (70). Intriguingly, genes associated with endocrine progenitor (Neurog3 and Mafb) and α-cells (Gcg and Arx) and δ-cells (Sst and Hhex) are upregulated in HFD-fed female β-cells, suggesting changes in cell identity. Male mice fed HFD exhibit higher expression of β-cell genes involved in protein secretion and cell proliferation, consistent with the well-established fact that male β-cells exhibit greater proliferation when fed HFD (71).

    Concluding Remarks

    We have identified many different genes and pathways in β-cells that are affected by metabolic stress. The broad-based nature of the changes we observe suggests that β-cell failure in T2D is not due to the failure of a single cellular process, but instead is a complex, multifaceted, and additive process in which Ca2+ signaling plays a crucial role.

    Article Information

    Acknowledgments. The authors thank the Vanderbilt Technologies for Advanced Genomics (VANTAGE) Core and the Vanderbilt University Medical Center Flow Cytometry Shared Resource for assistance in performing cell sorting and RNA sequencing and the Vanderbilt Islet Procurement and Analysis Core for help with isolating islets.

    Funding. This research was supported by institutional and philanthropic funds provided by Vanderbilt University. The Vanderbilt Islet Procurement and Analysis Core is supported by DK-020593. VANTAGE is supported by grants P30-CA-68485, P30-EY-08126, and G20-RR-030956. Vanderbilt University Medical Center Flow Cytometry Shared Resource is supported by grants P30-CA-68485 and DK-058404.

    Duality of Interest. No potential conflicts of interest relevant to this article were reported.

    Author Contributions. A.B.O. and M.A.M. designed the study. A.B.O., J.S.S., and K.D.D. performed experiments. A.B.O. analyzed the data. J.-P.C. performed RNA-sequencing data processing, alignment, and DE analyses. A.B.O. and M.A.M. wrote and edited the manuscript. J.S.S. edited the manuscript. M.A.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.



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    Butternut Squash Posole (Vegan, Gluten-free)

    By electricdiet / July 8, 2020


    This butternut squash posole combines sweet, spicy, and earthy flavors for a delicious vegan soup that will warm you right up!

    Butternut Squash Posole in a bowl topped with chopped avocado and cilantro

    This vegan butternut squash posole is a rich, hearty soup that’s easy to make and packed with amazing flavor!

    It’s a little bit sweet, a little bit spicy, a little bit earthy, and perfect to warm you up on a chilly day.

    Traditional posole (also spelled “pozole”) is a Mexican dish that features hominy, pork or chicken, chile peppers, and seasonings. This vegan recipe uses hearty vegetables and spices to get all that delicious flavor without the meat!

    If you’re looking for a rich soup packed with tasty veggies to fill you up, definitely give this easy recipe a try.

    How to make butternut squash posole

    This posole comes together in one pot on the stove with just a few simple steps!

    You can see how in this video and follow the step-by-step instructions below.

    Step 1: In a large Dutch oven or heavy-bottom pot, heat the oil over medium-high heat.

    Step 2: Stir in the chili powder, then immediately add the squash, chile peppers, oregano, cumin, garlic, and salt.

    Step 3: Cook, stirring frequently, until the peppers soften and the spices are evenly distributed over the squash, about 5 minutes.

    Step 4: Add water (or stock) and tomatoes, then cover and bring to a slow boil.

    Step 5: Uncover, reduce the heat to low, and simmer until the squash is tender, about 20 minutes.

    Step 6: Add the hominy and cook until warmed through, about 3 minutes.

    Step 7: Top with avocado before serving.

    Your delicious vegan posole is ready to enjoy! I like to garnish mine with cilantro for even more wonderful flavor.

    To reduce the sodium in this recipe, you can use no-salt-added canned tomatoes or skip the additional Kosher salt.

    What to serve with posole

    What goes well with a dish that features dried corn kernels as a main ingredient?

    More corn, of course!

    I love to serve vegan posole with a few tortilla chips. They provide an excellent crunch to contrast the soft vegetables.

    Or, if your carb count will allow it, a small piece of cornbread is fantastic for soaking up the soup’s flavor!

    If you’re looking for something a bit lighter, a green salad with orange vinaigrette would also be nice.

    Butternut Squash Posole in a bowl topped with chopped avocado and cilantro

    Is posole a soup or a stew?

    The main difference between a soup and a stew is how the dish is prepared. Specifically, a stew is made by stewing the ingredients — in other words, submerging the ingredients and simmering them in a covered pot until they are cooked through.

    Usually, a stew uses just enough liquid to cover the other ingredients. As it cooks, the liquid reduces, so a stew becomes very thick.

    This means that our vegan posole is probably more of a soup, which uses a good amount of liquid and simmers the ingredients to extract their flavor.

    Mexican-inspired posole may seem like a stew because of all the hearty ingredients. If you want, you can always add more water or broth to create a thinner soup.

    Storage

    Any leftover posole can be stored covered in the refrigerator. For maximum freshness, you should eat the rest of your soup within 4-5 days.

    You may notice that the flavors become even deeper and richer after sitting in the fridge overnight. That’s why I always try to make enough to have leftovers!

    Other healthy vegan recipes

    Vegan recipes can be so warm and comforting! If you’re looking for a few more hearty recipes that are packed with flavor and totally meat-free, here are some of my favorites that I know you’ll enjoy:

    When you’ve tried this posole, please don’t forget to let me know how you liked it and rate the recipe in the comments below!

    Recipe Card

    Butternut Squash Posole (Vegan, Gluten-free)

    Butternut Squash Posole

    This butternut squash posole combines sweet, spicy, and earthy flavors for a delicious vegan soup that will warm you right up!

    Prep Time:5 minutes

    Cook Time:25 minutes

    Total Time:30 minutes

    Author:Shelby Kinnaird

    Servings:4

    Instructions

    • In a large Dutch oven or heavy-bottom pot, heat the oil over medium-high heat.

    • Stir in the chili powder, then immediately add the squash, chile peppers, oregano, cumin, garlic, and salt.

    • Cook, stirring frequently, until the peppers soften and the spices are evenly distributed over the squash, about 5 minutes.

    • Add water (or stock) and tomatoes, then cover and bring to a slow boil.

    • Uncover, reduce the heat to low, and simmer until the squash is tender, about 20 minutes.

    • Add the hominy and cook until warmed through, about 3 minutes.

    • Top with avocado before serving.

    Recipe Notes

    This recipe is for 4 servings of posole. To reduce the sodium, use no-salt-added canned tomatoes or skip the additional Kosher salt. Leftovers can be stored covered in the refrigerator for 4-5 days.

    Nutrition Info Per Serving

    Nutrition Facts

    Butternut Squash Posole

    Amount Per Serving (0 g)

    Calories 270 Calories from Fat 131

    % Daily Value*

    Fat 14.5g22%

    Saturated Fat 2.7g17%

    Trans Fat 0g

    Polyunsaturated Fat 1.8g

    Monounsaturated Fat 9g

    Cholesterol 0mg0%

    Sodium 720.2mg31%

    Potassium 769.9mg22%

    Carbohydrates 31.2g10%

    Fiber 9.3g39%

    Sugar 7.6g8%

    Protein 4.7g9%

    Net carbs 21.9g

    * Percent Daily Values are based on a 2000 calorie diet.

    Course: Soups and Stews

    Cuisine: Mexican

    Diet: Diabetic, Gluten Free, Vegan

    Keyword: butternut squash posole, vegan posole, vegan recipes



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    Mock Mojito with Sugar Free Simple Syrup

    By electricdiet / July 6, 2020


    On July 1 I declared that July was going to be #dryjuly and give up alcohol for the month.  It corresponds with my DietBet that starts today (not too late to join! click here to get the details!)  and in order for me to lose 4%. of my body weight in four weeks (just over 7 pounds) I needed to ditch my beloved wine. 

    So Friday night I went to my friend Jacky’s house and had a BBQ with her husband and their friend.  It wouldn’t be a BBQ without some cheese and snacks, right? Jacky made jerk shrimp and melon nachos and I made this mini cheese board from cheese from Mariano’s, only my favorite grocery store in the world. 😀

    I knew I wanted to bring a mock tail and earlier in the day decided to see if I could make a sugar free simple syrup.  Only one tiny problem, is that sweeteners like Truvia dissolve, but they don’t really melt like sugar if you know what I mean.  So I decided to add corn starch to thicken it. 

    Once I let the mixture cool, it looked . . .really gross.  The corn starch kind of separated on the top, but I did get a syrup!  So I thought, why not strain it?  Which worked perfectly!  Once cooled I added the lime juice and zest.  This will keep in the fridge up to a week.

    Print

    Mock Mojito with Sugar Free Simple Syrup

    A great way to have a summer drink without alcohol.  My sugar free simple syrup was the perfect addition to lime zeltzer and fresh mint.


    Scale

    Ingredients

    1/2 cup water
    1/2 cup @truvia
    1 tablespoon cornstarch
    juice of 1 lime
    zest on one lime

    Instructions

    In a pan over medium heat. Mix the cornstarch with the water. Add that to the Truvia and bring to a low boil, stirring constantly. It should thicken up in about 5 minutes. Let cool. It’s going to look gross, so strain it into a mason jar. Once completely cool, stir in the juice and lime zest.

    Per drink: 2 teaspoons lime simple syrup to 1 can of lime seltzer. Add lime and fresh mint. Enjoy!

    Notes

    This drink is zero points on all WW plans.

    I bought not one but TWO tomahawks steaks to cook up this evening.  I brought one to Jacky’s house.   I get a bit nervous cooking on other people’s grills because I don’t know the hot spots, etc.  But it turned out perfect if I do say so myself!

    And not that I wasn’t happy to see Jacky, the best part was that she gave me her old bike!  She got a new one last year, and all I needed to do was to add air to the tires.  I rode for 30 minutes last night and it was awesome.  Thank you Jacky!

    On Saturday my Mom, Hannah and Jacob came over for another BBQ and another steak.  This time I was able to cook in indirect heat.  I cooked the steak until 115 degrees, then reverse seared it over the hot coals until it reached 120 degrees.

    My Mom slept over and we watched Hamilton on the big t.v.  – so good!  We slept in a bit and then Hannah and Jacob came over to mow my lawn and they brought the dogs over to visit.   I treated my Mom to a belated Mother’s Day gift pedicure and wow, did we need that!

    My feet have never felt better!

    After my Mom left, I took a 45 minute nap.  Um, someone (me) decided it was a good idea to drink coffee at 10:30 at night on Saturday while watching Hamilton (it would usually be wine!) so I had a hard time falling asleep.  

    But, I got up, did laundry, cleaned the kitchen and get ready for the work week.  Last week I drove to Chicago for the day to go to the office.  Um, I think I like my 10 second commute better though.

    Happy Monday friends.  I hope you had an amazing long weekend, and it’s never too late to make better choices.  I am proud that I have tracked everything, have been moving my body more.  It’s consistency not perfection that will get you to your goal – don’t forget that!

    Until next time….hugs!





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