Glucagon-like peptide 1-potentiated insulin secretion and proliferation of pancreatic β-cells.

Abstract

Glucagon-like peptide-1 (GLP-1) is the primary incretin hormone secreted from the intestine upon uptake of food to stimulate insulin secretion from pancreatic β-cells. GLP-1 exerts its effects by binding to its G-protein coupled receptors and subsequently activating adenylate cyclase, leading to generation of cyclic adenosine monophosphate (cAMP). cAMP stimulates insulin secretion via activation of its effectors PKA and Epac2 in pancreatic β-cells. In addition to its insulinotropic effects, GLP-1 also preserves pancreatic β-cell mass by stimulating β-cell proliferation. Unlike the action of sulphonylureas in lowering blood glucose levels, action of GLP-1 is affected by and interplays with glucose levels. Due to such advantages, GLP-1-based therapeutics have been rapidly developed and used clinically for treatment of type 2 diabetes. However, molecular mechanisms underlying how GLP-1 potentiates diminished glucose-stimulated insulin secretion and β-cell proliferation under diabetic conditions are not well understood. Here, we review the actions of GLP-1 in regulation of insulin secretion and pancreatic β-cell proliferation.