The major glucagon-like peptide-1 metabolite, GLP-1-(9-36)-amide, does not affect glucose or insulin levels in mice

Eur J Pharmacol. 2004 Jun 28;494(2-3):283-8. doi: 10.1016/j.ejphar.2004.05.013.

Abstract

Glucagon-like peptide-1 (GLP-1), a future treatment for type 2 diabetes, is efficiently degraded by the enzyme dipeptidyl peptidase IV (DPP IV), yielding the major metabolite GLP-1-(9-36)-amide. In this study, we examined the potential glucose lowering effect of GLP-1-(9-36)-amide in mice and found that GLP-1-(9-36)-amide (3 and 10 nmol/kg) did not affect insulin secretion or glucose elimination when administered intravenously together with glucose (1 g/kg). This was observed both in normal mice and in transgenic mice having a complete disruption of the signalling from the GLP-1 receptor. Furthermore, after blocking insulin secretion, using diazoxide (25 mg/kg), no effect on insulin-independent glucose disposal of GLP-1-(9-36)-amide was observed. Therefore, GLP-1-(9-36)-amide does not affect glucose disposal in mice either in the presence or absence of intact GLP-1-receptors or in the presence or absence of stimulated insulin levels. This suggests that the GLP-1 metabolite is not involved in the regulation of glucose homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Diazoxide / pharmacology
  • Female
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Injections, Intravenous
  • Insulin / blood*
  • Insulin / physiology
  • Islets of Langerhans / drug effects
  • Mice
  • Mice, Transgenic
  • Peptides / administration & dosage
  • Peptides / pharmacology*
  • Potassium Channels / agonists
  • Receptors, Glucagon / drug effects
  • Receptors, Glucagon / genetics

Substances

  • Blood Glucose
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Potassium Channels
  • Receptors, Glucagon
  • glucagon-like peptide-1 (9-36)-amide
  • Glucagon-Like Peptide 1
  • Diazoxide