Improved Glucose Tolerance via Enhanced Glucose-Dependent Insulin Secretion in Dipeptidyl Peptidase IV-deficient Fischer Rats

Biochem Biophys Res Commun. 2001 Jun 8;284(2):501-6. doi: 10.1006/bbrc.2001.4999.

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin, which induces glucose-dependent insulin secretion. GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. We investigated whether DPPIV-deficient F344/DuCrj rats show improved glucose tolerance when compared with DPPIV-positive F344/Jcl rats. Oral glucose tolerance test indicated improved glucose tolerance in F344/DuCrj rats, but blood glucose levels of the two strains were almost the same 120 min after the glucose bolus. Valine-pyrrolidide, a DPPIV inhibitor, had no effect on the glucose tolerance of F344/DuCrj rats, but improved that of F344/Jcl rats. Enhanced insulin secretion and high plasma active GLP-1 levels were detected in an intraduodenal glucose tolerance test. Glucose tolerance is improved in DPPIV-deficient F344/DuCrj rats via enhanced insulin release mediated by high active GLP-1 levels. Our results suggest that DPPIV inhibition is a rational strategy to treat diabetic patients by improving glucose tolerance with low risk of hypoglycemia.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / genetics
  • Dipeptidyl Peptidase 4 / drug effects
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism*
  • Duodenum / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glucagon / blood
  • Glucagon-Like Peptide 1
  • Glucose / administration & dosage
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Insulin / metabolism*
  • Insulin Secretion
  • Intubation, Gastrointestinal
  • Male
  • Peptide Fragments / blood
  • Protein Precursors / blood
  • Pyrroles / pharmacology
  • Rats
  • Rats, Inbred F344
  • Rats, Mutant Strains
  • Species Specificity
  • Valine / pharmacology

Substances

  • Blood Glucose
  • Enzyme Inhibitors
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Pyrroles
  • valine-pyrrolidide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Dipeptidyl Peptidase 4
  • Valine
  • Glucose