Chronic inhibition of dipeptidyl peptidase-IV with ASP8497 improved the HbA1c level, glucose intolerance, and lipid parameter level in streptozotocin–nicotinamide-induced diabetic mice

  • Akiko Matsuyama-Yokono
  • Atsuo Tahara
  • Ryosuke Nakano
  • Yuka Someya
  • Masahiko Hayakawa
  • Masayuki Shibasaki
Original Article

Abstract

Dipeptidyl peptidase-IV (DPP-IV) is the primary inactivator of glucoregulatory incretin hormones, and DPP-IV inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the chronic in vivo profile of the DPP-IV inhibitor ASP8497. In streptozotocin-nicotinamide-induced diabetic mice, ASP8497 was administered orally for 3 weeks at 1, 3, or 10 mg/kg once daily, which improved the hemoglobin A1c, non-fasting plasma insulin, fasting blood glucose levels, glucose intolerance, and lipid profiles (plasma triglyceride, non-esterified fatty acid and total cholesterol) with neutral effect on body weight. The pancreatic insulin content and hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity recovered dose-dependently in ASP8497-treated groups. These results revealed that ASP8497 was successful in improving glycemic control and metabolic parameters in streptozotocin-nicotinamide-induced diabetic mice. It is therefore suggested that ASP8497 may be a potential agent for the treatment of type 2 diabetes.

Keywords

ASP8497 Dipeptidyl peptidase-IV Glucagon-like peptide-1 Diabetes 

Notes

Acknowledgements

The authors would like to thank Drs. Toichi Takenaka, Isao Yanagisawa, Yasuaki Shimizu, Tetsuo Matsui, and Yutaka Yanagita (Astellas Pharma Inc.) for their valuable comments and continuing encouragement. The authors would also like to thank Mr. Masanori Yokono (Astellas Pharma Inc.) for his suggestions regarding the preparation of this manuscript.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Akiko Matsuyama-Yokono
    • 1
  • Atsuo Tahara
    • 1
  • Ryosuke Nakano
    • 1
  • Yuka Someya
    • 1
  • Masahiko Hayakawa
    • 1
  • Masayuki Shibasaki
    • 1
  1. 1.Drug Discovery ResearchAstellas Pharma Inc.IbarakiJapan

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