Suppr超能文献

长期暴露于格列本脲会损害分离的大鼠胰岛中的胰岛素分泌。

Chronic exposure to glibenclamide impairs insulin secretion in isolated rat pancreatic islets.

作者信息

Gullo D, Rabuazzo A M, Vetri M, Gatta C, Vinci C, Buscema M, Vigneri R, Purrello F

机构信息

Endocrinologia, University of Catania, Ospedale Garibaldi, Italy.

出版信息

J Endocrinol Invest. 1991 Apr;14(4):287-91. doi: 10.1007/BF03346813.

Abstract

We investigated the effect of 24 h exposure to 100 nmol/l glibenclamide on insulin secretion in isolated rat pancreatic islets. The insulin content was similar in control islets and in islets preincubated with 100 nmol/l glibenclamide for 24 h. In islets preexposed to glibenclamide: 1) the subsequent response to a maximal glibenclamide stimulatory concentration (10 mumol/l, 1 h at 37 C) was greatly reduced in comparison to control islets (0.69 +/- 0.20% vs 2.16 +/- 0.41%; mean +/- SE; n = 14; p less than 0.001); 2) the response to 100 mumol/l tolbutamide stimulation was also reduced (0.55 +/- 0.15% vs 2.38 +/- 0.44%; n = 8; p less than 0.001); 3) the response to 16.7 mmo/l glucose, both in the presence or in the absence of 1 mmol/l IBMX, a phosphodiesterase inhibitor, was also diminished by about 50% (1.79 +/- 0.39% vs. 3.22 +/- 0.42%; n = 14, p less than 0.001). In glibenclamide pretreated islets, blunted responses to stimuli were confirmed also by dynamic studies using a perifusion system. The effect of glibenclamide preincubation was fully reversible: when islets cultured in the presence of glibenclamide were transferred to a glibenclamide-free medium for further 24 h, insulin release in response to glibenclamide stimulation returned to control values. We conclude that prolonged exposure of rat pancreatic islets to glibenclamide induces a reversible desensitization to a variety of metabolic stimuli. The inhibition by prolonged glibenclamide exposure of a common pathway in the mechanism of insulin release is one possible explanation for these results.

摘要

我们研究了100纳摩尔/升格列本脲作用24小时对分离的大鼠胰岛胰岛素分泌的影响。对照胰岛和用100纳摩尔/升格列本脲预孵育24小时的胰岛中的胰岛素含量相似。在预先暴露于格列本脲的胰岛中:1)与对照胰岛相比,随后对最大格列本脲刺激浓度(10微摩尔/升,37℃孵育1小时)的反应大大降低(0.69±0.20%对2.16±0.41%;平均值±标准误;n = 14;p<0.001);2)对100微摩尔/升甲苯磺丁脲刺激的反应也降低(0.55±0.15%对2.38±0.44%;n = 8;p<0.001);3)在存在或不存在1毫摩尔/升磷酸二酯酶抑制剂异丁基甲基黄嘌呤(IBMX)的情况下,对16.7毫摩尔/升葡萄糖的反应也降低了约50%(1.79±0.39%对3.22±0.42%;n = 14,p<0.001)。在预先用格列本脲处理的胰岛中,使用灌流系统的动态研究也证实了对刺激反应的减弱。格列本脲预孵育的作用是完全可逆的:当在格列本脲存在下培养的胰岛转移到不含格列本脲的培养基中再培养24小时时,对格列本脲刺激的胰岛素释放恢复到对照值。我们得出结论,大鼠胰岛长时间暴露于格列本脲会导致对多种代谢刺激产生可逆的脱敏作用。长时间暴露于格列本脲对胰岛素释放机制中共同途径的抑制作用是这些结果的一种可能解释。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验