Inhibition of insulin degrading enzyme by racecadotril in the brain of wistar rats

J. P. Lee, K. C. Cheng, H. H. Chung, H. T. Wu, C. T. Chen, J. T. Cheng

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Racecadotril is an enkephalinase inhibitor used to treat abdominal discomfort in the clinic. The blood-glucose lowering action of racecadotril has been observed in rats; however, the mechanisms remain obscure. 8-week-old Wistar rats were intravenously injected with racecadotril and the levels of insulin in the brain were measured. Additionally, brain homogenates were co-incubated with racecadotril or thiorphan to evaluate insulin degrading enzyme (IDE) activity. Otherwise, rats were pretreated by intracerebroventricular (i.c.v.) injection of insulin antibody or glibenclamide at a dose sufficient to inhibit K ATP channels prior to injection of racecadotril. Moreover, rats were vagotomized to evaluate the role of the cholinergic nerve. Racecadotril significantly decreased the plasma glucose in rats; this action of racecadotril was abolished by i.c.v. pretreatment with insulin antibody or glibenclamide. Also, i.c.v. injection of thiorphan, the active form of racecadotril, lowered blood glucose, but this effect disappeared in the presence of the insulin antibody. In rat brain homogenates, racecadotril and thiorphan inhibited IDE activity and increased the cerebral insulin level. The blood-glucose lowering action of racecadotril or thiorphan was diminished in vagotomized rats. Our results suggest that racecadotril lowers blood glucose mainly through inhibition of IDE activity and increases endogenous insulin in the brain. Subsequently, the increased insulin might activate insulin receptor, which opens the K ATP channel and induces peripheral insulin release through the vagal nerve. Thus, we provide the new finding that racecadotril has the ability to inhibit IDE in rat brain.
原文英語
頁(從 - 到)489-493
頁數5
期刊Hormone and Metabolic Research
43
發行號7
DOIs
出版狀態已發佈 - 五月 11 2011
對外發佈Yes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

指紋 深入研究「Inhibition of insulin degrading enzyme by racecadotril in the brain of wistar rats」主題。共同形成了獨特的指紋。

引用此