The discovery could benefit millions of people worldwide.
A new discovery could be a game-changer for patients with type 2 diabetes. Researchers at the Diabetes, Obesity, and Metabolism Institute (DOMI) at the Icahn School of Medicine at Mount Sinai have discovered a therapeutic target for the preservation and regeneration of beta cells (β cells), the cells in the pancreas that produce and distribute insulin. The finding could also help millions of individuals throughout the globe by preventing insulin resistance. The study was recently published in the journal Nature Communications.
Insufficient ß – cell mass is the root cause of all major types of diabetes. When blood glucose levels in the body rise, such as in response to a high-fat diet, β cells respond by creating and releasing more insulin to manage blood glucose levels. Hyperglycemia, or persistently high blood glucose, may, however, hinder the ability of β cells to produce and secrete insulin. This leads to a vicious cycle of rising glucose levels and declining β–cell activity, which eventually ends in the death of β cells, a phenomenon known as glucose toxicity. Thus, β cell preservation and regeneration are therapeutic goals for diabetes.
The Mount Sinai researchers discovered a molecular mechanism involving carbohydrate response-element binding protein (ChREBP) that seems to be involved in β-cell preservation and regeneration. The researchers discovered that a hyperactive isoform of this protein, ChREBPβ, is required for the body to create more β cells in response to an elevated demand for insulin caused by a high-fat diet or significant glucose exposure. The overproduction of ChREBPβ, which leads to glucose toxicity in the β cells and eventual β cell death, might occur as a consequence of prolonged, increased glucose metabolism.
The research team found that it was possible to counteract the effects of ChREBPβ and the β-cell death they observed by increasing expression of an alternate form of the protein, ChREBP⍺, or by activating nuclear factor-erythroid factor 2 (Nrf2)—a protein that protects cells from oxidative damage—in mice and human β cells, thus preserving β-cell mass.
“Traditionally, ChREBP was thought to be a mediator of glucose toxicity, but we noticed one form, ChREBPa, appeared to protect beta cells,” said Donald Scott, Ph.D., a Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at Icahn Mount Sinai, and a member of DOMI and of The Mindich Child Health and Development Institute. “By using tools we developed that enabled us to interrogate these isoforms independently, we found that ChREBPβ plays a key role in the gradual destruction of β cells. Thus, we believe it is a marker of hyperglycemia and glucose toxicity.”
“Moreover, we found that if you remove ChREBPβ or counteract it pharmacologically, you can mitigate the effects of glucose toxicity and protect those cells. This exciting discovery creates an opportunity to develop therapeutic agents that target this molecular mechanism, effectively block ChREBPβ production, and thus preserve β-cell mass. This would not only address the challenge that has driven diabetes research for years but also prevents patients with type 2 diabetes from becoming insulin dependent due to loss of β-cell mass, which would have a significant impact on outcomes and quality of life.”
Based on these findings, the research team is interested in exploring the impact of ChREBPβ overproduction in patients with type 1 diabetes, which differs from type 2 diabetes in that the pancreas does not produce any insulin. The team is also interested in screening for more molecular mechanisms that have the potential to block ChREBPβ production and thus prevent glucose toxicity and the subsequent death of β cells. Furthermore, there are plans to investigate whether the vicious cycle that was observed in this study occurs in other tissues in which ChREBPβ is expressed, such as kidney, liver, and adipose, or body, fat, and thus might contribute to diabetic complications.
“This study was made possible by bringing together the full breadth of DOMI expertise in areas such as RNA sequencing, three-dimensional imaging, and bioinformatics. Our findings provide a foundation for preserving existing β-cell mass and for developing new therapeutic approaches that have the potential to successfully prevent thousands of type 2 diabetes patients from progressing to insulin dependence,” said the study’s lead author Liora S. Katz, Ph.D., Assistant Professor of Medicine at Icahn Mount Sinai.
Reference: “Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure” by Liora S. Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B. Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A. Stanley, Dirk Homann, Andrew F. Stewart, James C. Lo, Mark A. Herman, Adolfo Garcia-Ocaña and Donald K. Scott, 30 July 2022, Nature Communications.
Never be able to afford it.
Second paragraph wrong word used high fat should probably be high carbohydrate or high caloric. “ When blood glucose levels in the body rise, such as in response to a high-fat diet,…”
A high fat diet like keto was used to treat diabetes before exogenous insulin was available.
Margaret beat me to it….I too noticed the erroneous comment about a high fat diet. High fats do NOT raise blood sugar levels. It is a high carb diet that is the sole cause of type two diabetes and the obesity that accompanies it!!!! Whomever wrote this article needs to get their facts straight and stop feeding the mass information out there. I’ve been on a high fat/low carb/moderate protein diet for over a month now and tracking my blood glucose readings has shown a very low fluctuation in glucose readings with a “crude” A1C reading of approximately 4.9!
You would both be wrong. High fat is the correct term. Overconsumption of high amounts of fat can lead to obesity. Obesity then increases risk of diabetes type 2 due to insulin being fat-soluble and reducing the amount of available insulin to counter incoming glucose. This causes your body to overproduce insulin. Other forms of insulin resistance can occur, but by and large the greatest number of cases involve high fat diets that lead to obesity.
High carbohydrates is not the sole cause of diabetes and it shows your ignorance on the matter. Diabetes type 2 is caused by insulin resistance. Pure and simple. That can be caused by obesity and several other conditions, but obesity is the overwhelming majority of cases.
Ketosis was used to treat diabetes because it would essentially deprive the body of carbohydrates to the point that it would feed on fat instead, thus consuming the fat that comes in, instead of carbohydrates for energy. However, if you have a high fat diet, without depriving yourself of carbohydrates for energy, the excess fat gets stored in the body, causing obesity, eventually increasing insulin resistance. That’s why a lot of people in the early stages will “cute” their diabetes by significant weight loss.
Using low carbs and high fats only helps if if the fats you’re using are only good healthy fats, and not processed, saturated and other such fats, etc. If you stick with only healthy fats, then yes those diets are extremely helpful in lowering, if not eliminating type 2 diabetes.
I must comment again. The original Atkins Diet was not careful in regards to the particular fats you took in. It didn’t tell you to cut off all the fat on you steaks, etc. However, a modified version using, as I said earlier, only healthy fats, would make all the difference!!! And using such a low amount of crabs is to force your body to switch over to burning it’s Own Stored Fat, not to burn the fats you’re taking in, which should not be high, but the proper amount that your body needs, but of health fats like from nuts and such. I use an all Natural ‘I Can’t Believe It’s Not Butter’ that has no unhealthy fats, cholesterol, or anything else, in place of butter and it actually tastes fine. So with that diet you’re forced to burn your own fast stores, eat healthier fats, and slowly increase your carbs a little at a time as you like your weight until you’ve lost it all, and learned to eat healthier as well as improved your diabetes. And Sir, I would never insult your intelligence just because I felt you got something wrong. It could come back to bite you making you look foolish if it turned out that you might possibly have actually have misunderstood something yourself, like if perhaps the high fats people were eating that were part of the cause of the diabetes were unhealthy fats and that was what they meant( usually the case) , and they just didn’t clarify.
Everyone have a good day! 🙂
In my research back in 1990’s I found that the Ketogenic diet was developed at the Mayo Clinic in about 1920-1930’s for hard to treat epileptic cases. It was non specific on the types and amounts of fats that they recommended, even drinking cream instead of other liquids and so on.
Fat in your diet DOES NOT MAKE YOU FAT. SUGAR makes you FAT. All the excess energy of overdosing on sugar is stored as fat on your body. The ” manufactured” food in the U.S. and industrialized world in general is BOMBARDED with sugar. Just about EVERYTHING is infused with high fructose corn syrup. That’s what makes everyone fat. SUGAR. Sugar and carbohydrates.
I like fat a lots.
Mmmmm! Nothing more than gobblyguke. IF for some reason there was no more processed sugar on store shelves and your home pantry became empty of sugar the world stats on diabetes would plummet. The world has been addicted to processed sugar for over a hundred years. The processed sugar industries would go bankrupt as would the insulin manufacturers. Processed sugar is worse than narcotics. Blame human weakness.
Type 1 diabetes, commonly known as insulin-dependent diabetes mellitus (IDDM), is a type of diabetes that affects sugar metabolism. It is caused by the development of autoantibodies such as islet cell antibodies and insulin antibodies against beta-cell antigens by macrophages and T-lymphocytes. It usually starts in children and young people. As a result, it is also called as juvenile diabetes. Furthermore, the incidence of type 1 diabetes has increased in the last decade, affecting the young generation’s quality of life.
WOWWWWWWWWW IM SHOCKED!.. High fat diets DONT RAISE GLUCOSE LEVELS THEY REDUCE THEM….Who wrote this article??? eat a high fat carb free diet and watch your glucose levels go WAAAYYY down. Whoever wrote this article , never steped foot in ANY medical school thats for sure. high fat diets REDUCE blood glucose NOT increase it.