Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropyl- cyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: Comparison with voglibose and glibenclamide

Takao Ikenoue, Kyoko Okazaki, Shoji Fujitani, Yoshiharu Tsuchiya, Megumi Akiyoshi, Toshio Maki, Nobuo Kondo

研究成果: Article査読

52 被引用数 (Scopus)

抄録

(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an α-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose- dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats. However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose excursion. After sucrose loading, plasma insulin levels during the initial I h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early phase of insulin secretion.

本文言語English
ページ(範囲)354-359
ページ数6
ジャーナルBiological and Pharmaceutical Bulletin
20
4
出版ステータスPublished - 1997 4
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 薬理学、毒性学および薬学(全般)

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