title: Chronic inhibition of dipeptidyl peptidase-IV with ASP8497 improved the HbA(1c) level, glucose intolerance, and lipid parameter level in streptozotocin-nicotinamide-induced diabetic mice.
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 A(1c), 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.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 5-2-3, Toukoudai, Tsukuba, Ibaraki, Japan. akiko.matsuyama@jp.astellas.com
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsuyama-Yokono
authors.forename: Atsuo
authors.initials: A
authors.lastname: Tahara
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nakano
authors.forename: Yuka
authors.initials: Y
authors.lastname: Someya
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibasaki