Dipeptidyl Peptidase IV Inhibitor NVP-DPP728 Ameliorates Early Insulin Response and Glucose Tolerance in Aged Rats but Not in Aged Fischer 344 Rats Lacking Its Enzyme Activity

The Japanese Journal of Pharmacology

Hironobu Mitani¹  Misato Takimoto¹  Masaaki Kimura¹ 

[1] Research Division, Tsukuba Research Institute, Novartis Pharma K.K.

关键词: Dipeptidyl peptidase IV;    Fischer 344 rat;    Glucose tolerance;    Aging;    Diabetes;   

DOI  :  10.1254/jjp.88.451

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(14)The aim of this study was to investigate the effects of aging on glucose metabolism after oral glucose challenge in aged dipeptidyl peptidase IV (DPP-IV) positive (+) Fischer 344 (F344), DPP-IV deficient (−) F344 and DPP-IV(+) Wistar rats and to determine the effect of a DPP-IV inhibitor NVP-DPP728 (1-{2-[(5-cyanopyridin-2-yl)amino]ethylamino}acetyl-2-cyano-(S)-pyrrolidine monohydrochloride salt) on glucose tolerance in aged rats. Aging caused a decrease in early insulin response after an oral glucose challenge in aged Wistar or DPP-IV(+) F344 rats, but not in aged DPP-IV(−) F344 rats, compared with young control groups. Glucose tolerance after an oral glucose challenge in aged DPP-IV(−) F344 rats was better than in aged DPP-IV(+) F344 and Wistar rats associated with the preservation of the early insulin response. NVP-DPP728 improved the glucose tolerance after an oral glucose challenge by potentiating the early insulin response throughout the inhibition of plasma DPP-IV activity in aged DPP-IV(+) Wistar and F344 rats. In contrast, NVP-DPP728 did not affect the glucose tolerance after an oral glucose challenge in aged DPP-IV(−) F344 rats. These results indicate that treatment with NVP-DPP728 ameliorated glucose tolerance in aged rats by the direct inhibition of plasma DPP-IV activity and presumably the subsequent increase in endogenous incretin action.

【 授权许可】

Unknown