title: Glucagon-like peptide-1 structure, function and potential use for NIDDM.
abstract: 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 alpha-cells and a glucagon-like peptide-1 (GLP-1) in the intestine. GLP-1 is a hormone that is released by intestinal cells into the circulation in response to food intake. GLP-1 and gastric inhibitory peptide (GIP) which has also been termed glucose-dependent insulinotropic peptide appear to account for most of the incretin effect in the augmentation of glucose-stimulated insulin secretion. These two hormones have specific beta-cell receptors that are coupled to GTP binding proteins to induce production of cyclic AMP and activation of cyclic AMP-dependent protein kinase. It is proposed that at least one factor contributing to the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) is desensitization of the GLP-1 receptor on beta-cells. At pharmacological doses, infusion of GLP-1, but not of GLP, can improve and enhance postprandial insulin response in NIDDM patients. Agonists of GLP-1 receptor have been proposed as new potential therapeutic 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 present a unique advantage over sulfonylurea drugs in the treatment of NIDDM.
authors.affiliation: Department of Internal Medicine C, Barzilai Medical Center, Ashkelon, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Gefel
authors.forename: Y
authors.initials: Y
authors.lastname: Barg
authors.forename: R
authors.initials: R
authors.lastname: Zimlichman
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use*; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists*
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon