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A brand new examine from Duke College Faculty of Medication is difficult long-standing views on blood sugar regulation—and pointing to a stunning new ally within the combat towards sort 2 diabetes.
Revealed in Science Advances, the analysis reveals that pancreatic alpha cells, as soon as thought to solely produce glucagon—a hormone that raises blood sugar to keep up vitality when fasting or exercising—additionally generate GLP-1, a robust hormone that reinforces insulin and helps regulate glucose. GLP-1 is identical hormone mimicked by blockbuster medicine like Ozempic and Mounjaro.
Utilizing mass spectrometry, Duke researchers discovered that human alpha cells could naturally produce much more bioactive GLP-1 than beforehand believed.
Led by Duke scientist Jonathan Campbell, Ph.D., the crew of weight problems and diabetes researchers analyzed pancreatic tissue from each mice and people throughout a variety of ages, physique weights, and diabetes statuses. They discovered that human pancreatic tissue produces a lot greater ranges of bioactive GLP-1 and that this manufacturing is straight linked to insulin secretion.
“This research shows that alpha cells are more flexible than we imagined,” mentioned Campbell, an affiliate professor within the Division of Endocrinology within the Division of Medication and a member of the Duke Molecular Physiology Institute. “They can adjust their hormone output to support beta cells and maintain blood sugar balance.”
This flexibility may change how we take into consideration treating sort 2 diabetes, the place beta cells within the pancreas cannot make sufficient insulin to maintain blood sugar at a wholesome stage. By boosting the physique’s personal GLP-1 manufacturing, it could provide a extra pure option to help insulin and handle blood sugar.
Switching gears
In mouse research, when scientists blocked glucagon manufacturing, they anticipated insulin ranges to drop. As an alternative, alpha cells switched gears—ramping up GLP-1 manufacturing, enhancing glucose management, and triggering stronger insulin launch.
“We thought that removing glucagon would impair insulin secretion by disrupting alpha-to-beta cell signaling,” Campbell mentioned. “Instead, it improved it. GLP-1 took over, and it turns out, it’s an even better stimulator of insulin than glucagon.”
To check this additional, researchers manipulated two enzymes: PC2, which drives glucagon manufacturing, and PC1, which produces GLP-1. Blocking PC2 boosted PC1 exercise and improved glucose management. However when each enzymes had been eliminated, insulin secretion dropped and blood sugar spiked—confirming the crucial function of GLP-1.
Implications for diabetes remedy
Whereas GLP-1 is often made within the intestine, the examine confirms that alpha cells within the pancreas can even launch GLP-1 into the bloodstream after consuming, serving to to decrease blood sugar by rising insulin and decreasing glucagon ranges.
Frequent metabolic stressors, like a high-fat eating regimen, can enhance GLP-1 manufacturing in alpha cells—however solely modestly. That opens the door to future analysis: If scientists can discover methods to securely increase GLP-1 output from alpha cells, they are able to naturally improve insulin secretion in individuals with diabetes.
However measuring GLP-1 precisely hasn’t been simple. The crew developed a high-specificity mass spectrometry assay that detects solely the bioactive type of GLP-1—the model that really stimulates insulin—not the inactive fragments that always muddy outcomes.
“This discovery shows that the body has a built-in backup plan,” Campbell mentioned. “GLP-1 is simply a much more powerful signal for beta cells than glucagon. The ability to switch from glucagon to GLP-1 in times of metabolic stress may be a critical way the body maintains blood sugar control.”
Extra data:
Canqi Cui et al, Alpha-cells use each PC1/3 and PC2 to course of proglucagon peptides and management insulin secretion, Science Advances (2025). DOI: 10.1126/sciadv.ady8048. www.science.org/doi/10.1126/sciadv.ady8048
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Alpha cells moonlight as secret GLP-1 factories: Hormone shift may rework sort 2 diabetes remedy (2025, September 19)
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