March 4, 2021

Targeting glucagon action in diabetes

Disrupting the action of glucagon — a pancreatic hormone that works to raise blood glucose — restores functional insulin-producing cells in mouse models of type 1 diabetes and may be a promising treatment strategy.

Excess glucagon — a pancreatic hormone that works to raise blood glucose — contributes to metabolic dysregulation in diabetes. Targeted disruption of glucagon action is a potential treatment for diabetes. 

E. Danielle Dean, PhD, and colleagues explored the action of a glucagon receptor antagonist (Ab-4) in mouse models of type 1 diabetes.

They demonstrated improvements in blood glucose that persisted after a brief treatment ended. Ab-4 promoted survival of pancreatic beta cells and enhanced insulin-positive beta cell mass in part by conversion of pancreatic alpha cells to beta cells. Diabetic mice with human islet xenografts had improvements in glycemic control and increased human insulin secretion. 

The findings in mouse models of type 1 diabetes, reported in Proceedings of the National Academy of Sciencessupport a novel role for glucagon-targeted therapies in the treatment of diabetes to promote recovery of functional beta cell mass.

This research was supported by the National Institutes of Health (grants DK112866, DK117969, DK104211, DK112232, DK106755, DK020593, DK117147), Juvenile Diabetes Research Foundation and Department of Veterans Affairs.