Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L cells in response to ingested nutrients. The first recognized and most important action of GLP-1 is the potentiation of glucose-stimulated insulin secretion in beta-cells, mediated by activation of its seven transmembrane domain G-protein-coupled receptor. In addition to its insulinotropic actions, GLP-1 exerts islet-trophic effects by stimulating replication and differentiation and by decreasing apoptosis of beta-cells. The GLP-1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism, including pancreatic alpha-cells, hypothalamus and brainstem, and proximal intestinal tract. GLP-1 also appears to exert important actions in liver, muscle and fat. Thus, GLP-1 suppresses glucagon secretion, promotes satiety, delays gastric emptying and stimulates peripheral glucose uptake. The impaired GLP-1 secretion observed in type 2 diabetes suggests that GLP-1 plays a role in the pathogenesis of this disorder. Thus, because of its multiple actions, GLP-1 is an attractive therapeutic target for the treatment of type 2 diabetes, and major interest has resulted in the development of a variety of GLP-1 receptor agonists for this purpose. Ongoing clinical trials have shown promising results and the first analogs of GLP-1 are expected to be available in the near future.
De León
Diva D
DD
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.
Crutchlow
Michael F
MF
Ham
Jee-Young Nina
JY
Stoffers
Doris A
DA
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006706:Homeostasis; D006801:Humans; D000069450:Liraglutide; D008301:Maleimides / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009570:Nitriles / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists; D014688:Venoms / Q000627:therapeutic use
C121834:1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine; D001786:Blood Glucose; C473712:CJC 1131; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D008301:Maleimides; D009570:Nitriles; D010455:Peptides; D011480:Protease Inhibitors; D011759:Pyrrolidines; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D018819:Dipeptidyl Peptidase 4