Pancreatic Alpha Cells Offer Potential New Avenue for Type 2 Diabetes Treatment
Recent research from Duke University has revealed a surprising capacity within pancreatic alpha cells to produce significantly more of the hormone GLP-1 than previously understood. GLP-1 is a naturally occurring incretin hormone that stimulates insulin secretion and plays a crucial role in glucose regulation – the same mechanism targeted by popular diabetes medications like Ozempic and Mounjaro.
Led by Jonathan Campbell,PhD,Associate Professor in the Division of Endocrinology at Duke,the research team analyzed pancreatic tissue from both mice and humans across a range of ages,body weights,and diabetic statuses. Thier findings, utilizing a highly specific mass spectrometry technique developed by the team, demonstrated that human pancreatic tissue generates substantially higher levels of bioactive GLP-1 – the form directly responsible for stimulating insulin – than previously believed. This production was found to be directly correlated with insulin secretion.
“This research shows that alpha cells are more flexible than we imagine,” explained Dr. Campbell. “They can adjust their hormonal production to support beta cells and maintain the balance of blood sugar.”
the study also explored the interplay between glucagon, traditionally the primary hormone produced by alpha cells, and GLP-1. In mouse models, blocking glucagon production didn’t lead to the expected decrease in insulin. Instead, alpha cells responded by increasing GLP-1 production, resulting in improved glucose control and a stronger insulin release. Researchers manipulated the enzymes PC1 (responsible for GLP-1 production) and PC2 (responsible for glucagon production), finding that blocking PC2 increased PC1 activity and improved glucose control. Eliminating both enzymes, however, led to decreased insulin secretion and elevated blood sugar, highlighting the critical role of GLP-1.
While GLP-1 is commonly associated with intestinal production,this study confirms that alpha cells within the pancreas also release GLP-1 into circulation following food intake,contributing to lower blood sugar levels by boosting insulin and suppressing glucagon. The research also indicated that metabolic stressors, such as a high-fat diet, can modestly increase GLP-1 production in alpha cells.
These findings suggest a potential new therapeutic approach for type 2 diabetes, where beta cells struggle to produce sufficient insulin. By identifying ways to safely enhance GLP-1 release from alpha cells, scientists might potentially be able to naturally support insulin secretion and improve blood sugar management.
“This finding shows that the body has an integrated backup plan,” Dr. campbell concluded. “GLP-1 is simply a much more powerful signal for beta cells than glucagon.The ability to switch from glucagon to GLP-1 during metabolic stress can be a critical means of the body maintaining control of blood sugar.”
The research was supported by funding from the National Institutes of Health, Canadian Institutes of Health Research, Borden Scholars, and the Helmsley Charitable Trust Foundation. The study authors include Canqi Cui, Danielle C. Leander, Saraber, Kimber Grime, Pawgid, David, david A. Dueio, Tike; it Jessica O. Becker, Austin Taylor, Kyle W. Sloop, C. Bruce Vercher, and Andrew N. HoofNagle.