Project Grant R01DK148505

The National Institute of Diabetes and Digestive and Kidney Diseases awarded the University of California, Davis $782,890 on August 15, 2026, for Project Grant R01DK148505 under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847).

The research examines how alpha cells in the pancreas regulate glucose through distinct and sometimes opposing mechanisms during obesity and weight loss. Alpha cells overproduce glucagon in obesity and insulin resistance, stimulating hepatic glucose production and promoting type 2 diabetes development. Conversely, alpha cells enhance glucose-stimulated insulin secretion through paracrine communication with beta cells. The project investigates how this balance between hyperglycemic and hypoglycemic roles shifts under obesity and bariatric surgery, two conditions with major impacts on beta-cell function. The research addresses the critical need to understand glucagon's dual role under different metabolic conditions, particularly as novel glucagon agonists in development for weight loss must be combined with glucose-lowering drugs to achieve beneficial effects. Preliminary data demonstrates that both obesity and bariatric surgery increase circulating glucagon but produce opposing effects on glycemic regulation and the glucagon response to hypoglycemia.

Performance occurs in Davis, California, with work scheduled from August 15, 2026, through May 31, 2031.