灌注胰腺释放胰岛素对巯基的需求。用依他尼酸和二硫苏糖醇进行的研究。

Sulphydryl requirement for insulin release from the perfused pancreas. Studies with ethacrynic acid and dithiothreitol.

作者信息

Landgraf-Leurs M M, Mayer L, Landgraf R

出版信息

Diabetologia. 1978 Oct;15(4):337-42. doi: 10.1007/BF03160999.

Abstract

Using the isolated, perfused rat pancreas the importance of sulphydryl groups for the secretory process of insulin was investigated. It was found that ethacrynic acid (EA, 0.075-0.6 mmol/1) caused a dose-dependent, monophasic insulin release. Addition of EA to a glucose-stimulated (20 mmol/1) pancreas led to a sudden increase in hormone release, followed by a dose-dependent inhibition of release, which was not reversible after removal of EA. The same phenomenon was seen in the presence of 20 mmol/1 leucine. Dithiothreitol (DTT, 0.1 and 1 mmol/1) had no effect on basal insulin secretion. Added to a glucose-stimulated pancreas DTT (1 mmol/1) caused a reversible inhibition of insulin release. The persistent inhibitory action of EA on glucose-induced insulin release could be reversed by simultaneous perfusion of EA and DTT. Sequential exposure of a glucose-stimulated pancreas to EA and DTT led to a rapid release of insulin, due to DTT; however, the EA-induced inhibition of insulin secretion could not be prevented. Two kinds of thiol groups in the plasma membrane and in the beta cell might be responsible for the various kinetics of insulin release induced by EA and DTT.

摘要

利用离体灌注大鼠胰腺，研究了巯基对胰岛素分泌过程的重要性。发现依他尼酸（EA，0.075 - 0.6 mmol/1）引起剂量依赖性的单相胰岛素释放。将EA添加到葡萄糖刺激（20 mmol/1）的胰腺中会导致激素释放突然增加，随后是剂量依赖性的释放抑制，去除EA后这种抑制不可逆。在存在20 mmol/1亮氨酸的情况下也观察到相同现象。二硫苏糖醇（DTT，0.1和1 mmol/1）对基础胰岛素分泌无影响。将DTT（1 mmol/1）添加到葡萄糖刺激的胰腺中会引起胰岛素释放的可逆抑制。EA对葡萄糖诱导的胰岛素释放的持续抑制作用可通过同时灌注EA和DTT来逆转。将葡萄糖刺激的胰腺先后暴露于EA和DTT会由于DTT导致胰岛素快速释放；然而，EA诱导的胰岛素分泌抑制无法预防。质膜和β细胞中的两种巯基可能负责EA和DTT诱导的胰岛素释放的不同动力学。