Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice

Ahrén B., Holst J., Mårtensson H., KUVAKİ BALKAN B.

EUROPEAN JOURNAL OF PHARMACOLOGY, cilt.404, sa.1-2, ss.239-245, 2000 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 404 Sayı: 1-2
  • Basım Tarihi: 2000
  • Doi Numarası: 10.1016/s0014-2999(00)00600-2
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.239-245
  • Anahtar Kelimeler: dipeptidyl peptidase IV, glucagon-like peptide-1 (GLP-1), insulin secretion, glucose tolerance, diabetes, type 2, glucose tolerance, impaired
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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 mu mol/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 CLP-I 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. (C) 2000 Elsevier Science B.V. All rights reserved.