Incretins
Updated January 15, 2025
Hormones and Metabolism Program
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Incretins are “peptide” hormones made by the small intestines that have effects on hunger and insulin release. Pharmaceutical analogues are growing in popularity due to their effect on weight, metabolism and hunger. They were approved in June 2021 by the FDA for use for weight management.
The GLP-1 Agonists, (a separate post) starting with Byetta in 2005 are recently making the waves due to their ability to impact upon obesity (i.e. the latest greatest weight loss drugs). There are huge controversies about their pricing, their politics and good and bad effects). Only in the USA are they approved for children starting at the age of 12. Whether they have to be taken long-term remains unknown.
FDA Approves New Drug Treatment for Chronic Weight Management_2021_06
The New Side of Incretin-Based Therapy in Type 2 Diabetes–Exploring Advances From EASD 2021
The New Side of Incretin-Based Therapy in Type 2 Diabetes–Exploring Advances From EASD 2021
New Insights Into the Role of Incretins in the Treatment of Diabetes.2005
Mark Hyman Podcast about low-dose GLP-1 Agonists
Tyna Moore ND Podcasts, several on GLP-1 low dose
pending
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From Open AI 4/7/2023
Incretins are hormones produced by the gut in response to food intake that stimulate insulin secretion from the pancreas, thereby regulating blood glucose levels. The two main incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (1).
GLP-1 is a peptide hormone produced by the L cells of the small intestine in response to nutrient ingestion (2). Once secreted, GLP-1 binds to its receptor on the beta cells of the pancreas, causing an increase in the release of insulin. GLP-1 also inhibits glucagon secretion from the alpha cells of the pancreas, slows gastric emptying, reduces appetite, and promotes beta cell growth and survival (3).
GIP is another hormone produced by the K cells of the small intestine in response to nutrient ingestion. Like GLP-1, GIP stimulates insulin secretion from the beta cells of the pancreas (4). However, unlike GLP-1, GIP has little effect on glucagon secretion, gastric emptying, or appetite (5).
Because of their effects on glucose metabolism, incretin-based therapies have been developed for the treatment of type 2 diabetes. GLP-1 receptor agonists are a class of drugs that mimic the effects of GLP-1. They bind to the GLP-1 receptor on the beta cells of the pancreas, causing an increase in the release of insulin. GLP-1 receptor agonists also have other beneficial effects on glucose metabolism, such as slowing gastric emptying, reducing appetite, and promoting beta cell growth and survival (6). Examples of GLP-1 receptor agonists include exenatide (Byetta), liraglutide (Victoza), and dulaglutide (Trulicity).
Dipeptidyl peptidase-4 (DPP-4) inhibitors are another class of drugs used to treat type 2 diabetes. DPP-4 is an enzyme that degrades GLP-1, thereby reducing its half-life. DPP-4 inhibitors block the action of DPP-4, leading to an increase in the half-life of endogenous GLP-1 (7). This results in an increase in insulin secretion from the beta cells of the pancreas. Examples of DPP-4 inhibitors include sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta).
In summary, incretins are hormones produced by the gut in response to food intake that stimulate insulin secretion from the pancreas, thereby regulating blood glucose levels. GLP-1 and GIP are the two main incretin hormones. Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, are used to treat type 2 diabetes by enhancing the effects of endogenous incretin hormones.
Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care. 2003 Mar;26(3):292-8. doi: 10.2337/d
From Open AI 4/7/2023
Are there plant-based molecules that act like incretins
Yes, there are plant-based molecules that act like incretins in the body. One example is , a natural compound found in several plants including Berberis vulgaris, which has been shown to have antidiabetic properties and improve glucose tolerance in animal models (1, 2). Berberine has been shown to activate the GLP-1 receptor and stimulate insulin secretion, similar to GLP-1 receptor agonists (3).
Another example is resveratrol, a polyphenolic compound found in several plants, including grapes and red wine. Resveratrol has been shown to improve glucose metabolism and insulin sensitivity in animal models and humans, and has been proposed as a potential therapeutic agent for the treatment of type 2 diabetes (4). Resveratrol has also been shown to increase GLP-1 secretion and improve GLP-1 receptor signaling in the intestine (5).
Research is ongoing to better understand the potential benefits of these plant-based incretin mimetics and to explore their potential as therapeutic agents for the treatment of type 2 diabetes.
References:
Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008 Jul;93(7):2559-65. doi: 10.1210/jc.2007-2404.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013.
Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G, Vonderfecht S, Hecht R, Li YS, Lindberg RA, Chen JL, Jung DY, Zhang Z, Ko HJ, Kim JK, Véniant MM. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes. 2009 Apr;58(1):250-9. doi: 10.2337/db08-0392.
Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MK, Kunz I, Schrauwen-Hinderling VB, Blaak EE, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612-22. doi: 10.1016/j.cmet.2011.10.002.
Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Jul;106(3):383-9. doi: 10.1017/S0007114511000316.
From Open AI 4/7/2023
what happens if you give a GLP-1 agonist to a person with type 1 diabetes
GLP-1 receptor agonists are primarily used for the treatment of type 2 diabetes, but they have also been studied in the context of type 1 diabetes. In people with type 1 diabetes, the beta cells of the pancreas that produce insulin are destroyed, and the body is unable to produce enough insulin to regulate blood glucose levels. GLP-1 receptor agonists stimulate insulin secretion from the remaining beta cells of the pancreas, and can also slow gastric emptying and reduce appetite, leading to improved glycemic control.
However, GLP-1 receptor agonists are not currently approved for use in people with type 1 diabetes, and their use in this population is still being studied. One concern is that GLP-1 receptor agonists may increase the risk of hypoglycemia, especially when used in combination with insulin (1).
Another potential issue is that GLP-1 receptor agonists may have different effects on the immune system in people with type 1 diabetes compared to those with type 2 diabetes. GLP-1 receptor agonists have been shown to have immunomodulatory effects, and there is some evidence that they may have a beneficial effect on autoimmunity in type 1 diabetes (2). However, more research is needed to fully understand the potential benefits and risks of GLP-1 receptor agonists in people with type 1 diabetes.
In summary, GLP-1 receptor agonists have been studied in people with type 1 diabetes, but their use in this population is still being investigated. They may have potential benefits for glycemic control and autoimmunity, but there are also concerns about hypoglycemia and the effects of GLP-1 receptor agonists on the immune system in people with type 1 diabetes.
References:
Mathieu C, Zinman B, Hemmingsson JU, Woo V, Colman P. Safety and efficacy of liraglutide added to insulin treatment in type 1 diabetes: The ADJUNCT ONE treat-to-target randomized trial. Diabetes Care. 2016 Mar;39(3):1702-10. doi: 10.2337/dc15-1990.
Hu Y, Peng J, Li F, Wong FS, Wen L. Evaluation of different therapeutic agents on the modulation of regulatory T cells in type 1 diabetic mice. Clin Immunol. 2011 Apr;139(1):58-65. doi: 10.1016/j.clim.2011.01.007.
