The biology of incretin hormones.
Gut peptides, exemplified by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted in a nutrient-dependent manner and stimulate glucose-dependent insulin secretion. Both GIP and GLP-1 also promote beta cell proliferation and inhibit apoptosis, leading to expansion of beta cell mass. GLP-1, but not GIP, controls glycemia via additional actions on glucose sensors, inhibition of gastric emptying, food intake and glucagon secretion. Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes. This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes.
Drucker
Daniel J
DJ
Department of Medicine, The Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Ontario M5G 2C4, Canada. d.drucker@utoronto.ca
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism
D005768:Gastrointestinal Hormones; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1