Insulin-like actions of glucagon-like peptide-1: a dual receptor hypothesis

Trends Endocrinol Metab. 2010 Feb;21(2):59-67. doi: 10.1016/j.tem.2009.11.007. Epub 2009 Dec 16.

Abstract

GLP-1 (9-36)amide is the cleavage product of GLP-1(7-36) amide, formed by the action of diaminopeptidyl peptidase-4 (Dpp4), and is the major circulating form in plasma. Whereas GLP-1(7-36)amide stimulates glucose-dependent insulin secretion, GLP-1(9-36)amide has only weak partial insulinotropic agonist activities on the GLP-1 receptor, but suppresses hepatic glucose production, exerts antioxidant cardioprotective actions and reduces oxidative stress in vasculature tissues. These insulin-like activities suggest a role for GLP-1 (9-36)amide in the modulation of mitochondrial functions by mechanisms independent of the GLP-1 receptor. In this paper, we discuss the current literature suggesting that GLP-1(9-36)amide is an active peptide with important insulin-like actions. These findings have implications in nutrient assimilation, energy homeostasis, obesity, and the use of Dpp4 inhibitors for the treatment of diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Glucagon-Like Peptide 1 / chemistry
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide-1 Receptor
  • Heart / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Insulin / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Models, Biological
  • Models, Theoretical
  • Molecular Sequence Data
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Processing, Post-Translational / physiology
  • Receptor, Insulin / metabolism
  • Receptor, Insulin / physiology*
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism
  • Receptors, Glucagon / physiology*

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Peptide Fragments
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Receptor, Insulin