GLUCAGON-LIKE PEPTIDE-1 STRUCTURE, FUNCTION AND POTENTIAL USE FOR NIDDM

Basic research on the cellular mechanisms that control the expression of the gene encoding glucagon has led to the discovery of proglucagon. This precursor is processed by tissue-specific proteolysis to produce glucagon in pancreatic ct-cells and a glucagon-like peptide-1 (GLP-1) in the intestine, GLP-1 is a hormone that is released by intestinal c ells into the circulation in response to food intake. GLP-1 and gastri c inhibitory peptide (GlP) which has also been termed glucose-dependen t insulinotropic peptide appear to account for most of the incretin ef fect in the augmentation of glucose-stimulated insulin secretion, Thes e two hormones have specific beta-cell receptors that are coupled to G TP binding proteins to induce production of cyclic BMP and activation of cyclic AMP-dependent protein kinase. it is proposed that at least o ne factor contributing to the pathogenesis of non-insulin-dependent di abetes mellitus (NIDDM) is desensitization of the GLP-1 receptor on be ta-cells. At pharmacological doses, infusion of GLP-1, but not of GLP, can improve and enhance postprandial insulin response in NIDDM patien ts. Agonists of GLP-1 receptor have been proposed as new potential the rapeutic agents in NIDDM patients. The observations that GLP-1 induces both secretion and production of insulin, and that its activities are mainly glucose-dependent, led to the suggestion that GLP-1 may presen t a unique advantage over sulfonylurea drugs in the treatment of NIDDM .