Study Points To A Surprising New Ally In The Fight Against Type 2 Diabetes

A caller study from Duke University School of Medicine is challenging long-standing views connected humor sweetener regularisation - and pointing to a astonishing caller state successful nan conflict against type 2 diabetes.

Published Sept. 19 successful Science Advances, nan investigation reveals that pancreatic alpha cells, erstwhile thought to only nutrient glucagon - a hormone that raises humor sweetener to support power erstwhile fasting aliases exercising - besides make GLP-1, a powerful hormone that boosts insulin and helps modulate glucose. GLP-1 is nan aforesaid hormone mimicked by blockbuster narcotics for illustration Ozempic and Mounjaro.

Using wide spectrometry, Duke researchers recovered that quality alpha cells whitethorn people nutrient acold much bioactive GLP-1 than antecedently believed.

Led by Duke intelligence Jonathan Campbell, PhD, nan squad of obesity and glucosuria researchers analyzed pancreatic insubstantial from some mice and humans crossed a scope of ages, assemblage weights, and glucosuria statuses. They recovered that quality pancreatic insubstantial produces overmuch higher levels of bioactive GLP-1 and that this accumulation is straight linked to insulin secretion.

This investigation shows that alpha cells are much elastic than we imagined. They tin set their hormone output to support beta cells and support humor sweetener balance."

Jonathan Campbell, PhD, subordinate professor, Division of Endocrinology, Department of Medicine and member of the Duke Molecular Physiology Institute

This elasticity could alteration really we deliberation astir treating type 2 diabetes, wherever beta cells successful nan pancreas can't make capable insulin to support humor sweetener astatine a patient level. By boosting nan body's ain GLP-1 production, it whitethorn connection a much earthy measurement to support insulin and negociate humor sugar.

Switching gears

In rodent studies, erstwhile scientists blocked glucagon production, they expected insulin levels to drop. Instead, alpha cells switched gears - ramping up GLP-1 production, improving glucose control, and triggering stronger insulin release.

"We thought that removing glucagon would impair insulin secretion by disrupting alpha-to-beta cell signaling," Campbell said. "Instead, it improved it. GLP-1 took over, and it turns out, it's an moreover amended stimulator of insulin than glucagon."

To trial this further, researchers manipulated 2 enzymes: PC2, which drives glucagon production, and PC1, which produces GLP-1. Blocking PC2 boosted PC1 activity and improved glucose control. But erstwhile some enzymes were removed, insulin secretion dropped and humor sweetener spiked - confirming nan captious domiciled of GLP-1.

Implications for glucosuria treatment

While GLP-1 is typically made successful nan gut, nan study confirms that alpha cells successful nan pancreas tin besides merchandise GLP-1into nan bloodstream aft eating, helping to little humor sweetener by expanding insulin and reducing glucagon levels.

Common metabolic stressors, for illustration a high-fat diet, tin summation GLP-1 accumulation successful alpha cells - but only modestly. That opens nan doorway to early research: If scientists tin find ways to safely boost GLP-1 output from alpha cells they whitethorn beryllium capable to people heighten insulin secretion successful people pinch diabetes.

But measuring GLP-1 accurately hasn't been easy. The squad developed a high-specificity wide spectrometry assay that detects only nan bioactive shape of GLP-1 - nan type that really stimulates insulin - not nan inactive fragments that often muddy results.

"This find shows that nan assemblage has a built-in backup plan," Campbell said. "GLP-1 is simply a overmuch much powerful awesome for beta cells than glucagon. The expertise to move from glucagon to GLP-1 successful times of metabolic accent whitethorn beryllium a captious measurement nan assemblage maintains humor sweetener control."

Additional authors: Canqi Cui, Danielle C. Leander, Sarah M. Gray, Kimberly El, Alex Chen, Paul Grimsrud, Guo-Fang Zhang, David A. D'Alessio, each of Duke; and Jessica O. Becker, Austin Taylor, Kyle W. Sloop, C. Bruce Verchere, and Andrew N. Hoofnagle,

Funding: National Institutes of Health, Canadian Institutes of Health Research, Borden Scholars, and Helmsley Charitable Trust Foundation.