Improved Glucose Tolerance and Insulin Secretion by Inhibition of Dipeptidyl Peptidase IV in Mice

Eur J Pharmacol. 2000 Sep 15;404(1-2):239-45. doi: 10.1016/s0014-2999(00)00600-2.

Abstract

We explored whether inhibition of the enzyme dipeptidyl peptidase IV (DPP IV) increases endogenous levels of glucagon-like peptide-1 (GLP-1) and improves glucose tolerance and insulin secretion in mice. Glucose (150 mg) was administered through a gastric gavage with or without the inhibitor of dipeptidyl peptidase IV, valine-pyrrolidide (100 micromol/kg), in high-fat fed glucose intolerant or control C57BL/6J mice. The increase in plasma GLP-1 after gastric glucose was potentiated by dipeptidyl peptidase IV inhibition (P<0.05). Valine-pyrrolidide also potentiated the plasma insulin response to gastric glucose and improved the glucose tolerance in both groups of mice (P<0.001). In contrast, valine-pyrrolidide did not affect glucose-stimulated insulin secretion from isolated islets. This suggests that valine-pyrrolidide improves insulin secretion and glucose tolerance through indirect action, probably through augmentation of levels of GLP-1 and other incretin hormones. Therefore, inhibition of dipeptidyl peptidase IV activity is feasible to exploit as a treatment for glucose intolerance and type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Body Weight
  • Dipeptidyl Peptidase 4 / metabolism*
  • Female
  • Glucagon / blood
  • Glucagon-Like Peptide 1
  • Glucose / physiology*
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / blood
  • Protease Inhibitors / pharmacology
  • Protein Precursors / blood

Substances

  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Protease Inhibitors
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Dipeptidyl Peptidase 4
  • Glucose