Insulin secretagogues with an imidazoline structure inhibit arginine-induced glucagon secretion from isolated rat islets of Langerhans

被引:12
作者
Mourtada, M
Smith, SA
Morgan, NG
机构
[1] UNIV KEELE,DEPT BIOL SCI,CELLULAR PHARMACOL GRP,KEELE ST5 5BG,STAFFS,ENGLAND
[2] SMITHKLINE BEECHAM PHARMACEUT,HARLOW CM19 5AD,ESSEX,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1006/bbrc.1997.6922
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is well documented that imidazoline compounds such as efaroxan and phentolamine act as potent insulin secretagogues both in vivo and in vitro, an effect which is mediated principally by blockade of ATP-sensitive potassium channels in the pancreatic B-cell, However, little is known about the effects of these drugs on the secretion of other pancreatic hormones and, in the present work, we have investigated the effects of selective imidazoline compounds on glucagon release from isolated rat islets of Langerhans, None of several imidazoline compounds tested (efaroxan, phentolamine, idazoxan, antazoline) affected glucagon secretion from isles incubated with 4mM glucose. However, when the rate of glucagon release was stimulated by L-arginine (20mM) efaroxan caused a rapid, sustained and dose-dependent inhibition of the secretary response (EC50 approximately 30 mu M). This effect was seen under both static incubation and islet perifusion conditions. Antazoline and phentolamine also inhibited arginine-induced glucagon secretion, whereas idazoxan (an imidazoline which does not affect insulin secretion) failed to alter glucagon release, The inhibitory effects of imidazolines on glucagon release were neat secondary to changes in insulin secretion. Taken together, the results indicate that pancreatic A-cells express functional imidazoline receptors which can regulate the secretory activity of the cells. (C) 1997 Academic Press.
引用
收藏
页码:162 / 166
页数:5
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