Glucagon-like peptide-1, glucose homeostasis and diabetes

Incretins, enhancers of insulin secretion, are essential for glucose tolerance, and a reduction in their function might contribute to poor β-cell function in patients with type-2 diabetes mellitus. However, at supraphysiological doses, the incretin glucagon-like peptide-1 (GLP-1) protects pancreatic β cells, and inhibits glucagon secretion, gastric emptying and food intake, leading to weight loss. GLP-1 mimetics, which are stable-peptide-based activators of the GLP-1 receptor, and incretin enhancers, which inhibit the incretin-degrading enzyme dipeptidyl peptidase-4, have emerged as therapies for type-2 diabetes and have recently reached the market. The pathophysiological basis the clinical use of these therapeutics is reviewed here.