Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus

Int J Biochem Cell Biol. 2006;38(5-6):845-59. doi: 10.1016/j.biocel.2005.07.011. Epub 2005 Sep 15.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / etiology*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / etiology
  • Dipeptidyl Peptidase 4 / metabolism
  • Exenatide
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide 1 / therapeutic use*
  • Glucagon-Like Peptide-1 Receptor
  • Homeostasis
  • Humans
  • Liraglutide
  • Maleimides / therapeutic use
  • Molecular Sequence Data
  • Nitriles / therapeutic use
  • Peptides / therapeutic use
  • Protease Inhibitors / therapeutic use
  • Pyrrolidines / therapeutic use
  • Receptors, Glucagon / agonists
  • Venoms / therapeutic use

Substances

  • 1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine
  • Blood Glucose
  • CJC 1131
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Maleimides
  • Nitriles
  • Peptides
  • Protease Inhibitors
  • Pyrrolidines
  • Receptors, Glucagon
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide
  • Dipeptidyl Peptidase 4