ABSTRACT
Incretins are gut hormones that are released from gut endocrine cells following oral ingestion of nutrients. The incretin hormones include glucagon-like peptide-1 (GLP-1) and lucosedependentinsulinotropic polypeptide (GIP). GIP and GLP-1 are jointly responsible for the socalled incretin effect. That is, oral administration of an amount of glucose causes a greater stimulus of insulin secretion than the same amount of glucose administered by the intravenous route. Both incretins potentiate glucose-dependent insulin secretion and enhance beta-cell massthrough regulation of beta-cell proliferation, neogenesis and apoptosis. In contrast, GLP-1, but not GIP, inhibits gastric emptying, glucagon secretion, and food intake. The incretins share similar effects on the pancreatic beta cell; however, there are a number of differences in extrapancreatic actions. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4(DPP4). Type 2 diabetes mellitus (T2DM) is associated with abnormal incretin physiology, the incretin effect is severely reduced or absent. In patients with T2DM the secretion of GIP is nearnormal, but its effect on insulin secretion is severely impaired. GLP-1 secretion, on the other hand, is also impaired, but its insulinotropic action is preserved, although the potency of GLP-1 in this respect is decreased compared to healthy subjets.