GLP-1 in NIDDM

Abstract

Glucagon-like peptide-1 (GLP-1), a product of intestinal expression of the glucagon gene, is a potent insulinotropic hormone released in response to ingestion of meals. Specific GLP-1 receptors, G-protein coupled receptors that activate adenylate cyclase are located in the pancreatic islets and also in brain and various other tissues. GLP-1 also inhibits glucagon secretion and therefore inhibits hepatic glucose production and decreases blood glucose. However, as its effects on insulin secretion are glucose dependent, its effect on blood glucose in self-limiting. Because of these actions GLP-1 administration can completely normalize the hyperglycaemia of NIDDM without a risk of hypoglycaemia and GLP-1 is therefore currently considered as a therapeutic agent. GLP-1 also inhibits gastrointestinal secretion and motility, presumably via interaction with cerebral receptors. This effect may help curtail meal-induced glucose excursions, but may also limit its use. Being a peptide GLP-1 requires parenteral administration, but because of rapid enzymatic degradation its bioavailability is low. Current research efforts are aimed at the development of orally active GLP-1 analogues.