Naunyn-Schmiedeberg's Archives of Pharmacology

, 379:191

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


    • Drug Discovery ResearchAstellas Pharma Inc.
  • Atsuo Tahara
    • Drug Discovery ResearchAstellas Pharma Inc.
  • Ryosuke Nakano
    • Drug Discovery ResearchAstellas Pharma Inc.
  • Yuka Someya
    • Drug Discovery ResearchAstellas Pharma Inc.
  • Masahiko Hayakawa
    • Drug Discovery ResearchAstellas Pharma Inc.
  • Masayuki Shibasaki
    • Drug Discovery ResearchAstellas Pharma Inc.
Original Article

DOI: 10.1007/s00210-008-0348-x

Cite this article as:
Matsuyama-Yokono, A., Tahara, A., Nakano, R. et al. Naunyn-Schmied Arch Pharmacol (2009) 379: 191. doi:10.1007/s00210-008-0348-x


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.


ASP8497Dipeptidyl peptidase-IVGlucagon-like peptide-1Diabetes

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© Springer-Verlag 2008