GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival.
Type 2 diabetes is a metabolic disorder characterized by insulin resistance as well as a progressive deterioration of pancreatic beta-cell mass and function. Glucagon-like peptide 1 (GLP-1), an incretin hormone secreted by intestinal L cells, is a promising therapeutic agent in the treatment of diabetes. GLP-1 analogs and enhancers constitute a novel class of anti-diabetes medications which address both the insulin secretion defect as well as the decline in beta-cell mass. GLP-1 improves glucose-stimulated insulin secretion, restores glucose competence in glucose-resistant beta-cells, and stimulates insulin gene expression and biosynthesis. Furthermore, GLP-1 acts as a growth factor by promoting beta-cell proliferation, survival and neogenesis. This review focuses on the molecular mechanisms by which GLP-1 signaling induces beta-cell mass expansion.
Buteau
J
J
Department of Anatomy and Physiology, Université Laval and Centre de Recherche de l'Hôpital Laval, 2725 Ch. Ste-Foy, Y-3120, Quebec, QC G1V 4G5, Canada. jean.buteau@crhl.ulaval.ca
D002455:Cell Division; D002470:Cell Survival; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects; D011480:Protease Inhibitors / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000502:physiology*; D015398:Signal Transduction
D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D011480:Protease Inhibitors; D018027:Receptors, Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4