双孔钾通道KCNKl6在大鼠胰岛中的表达及调节  

Expression and regulation of a two-pore domain K＋ channel KCNK16 in rat islets

作　　者：张玉青[1] 杨雪[1] 王晓[1] 唐红菊[1] 邓儒元[1] 刘赟[1] 李凤英[1] 王瑶[1] 许琬[1] 纪雪莹 周丽斌[1] 

机构地区：[1]上海市内分泌代谢病研究所,上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,200025

出　　处：《中华内分泌代谢杂志》2015年第5期452-456,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目（81170720,81270910,81370876）;上海市卫生局局级课题（20114278）

摘　　要：目的观察双孔钾通道KCNKl6在大鼠胰岛中的表达情况，并探讨促进G细胞胰岛素分泌的刺激因素对其表达的调节。方法采用实时定量PCR和组织化学染色技术观察KCNKl6在大鼠胰岛及其他组织中的表达。分别用葡萄糖、催乳素、软脂酸以及曲古菌素A（TrichostatinA．TSA）处理大鼠胰岛24h，实时定量PCR和Western印迹法检测KCNKl6的表达水平。以ELISA检测TSA处理大鼠胰岛24h后葡萄糖和KCl刺激的胰岛素分泌水平。不同浓度和时间的TSA处理INSl-E细胞．实时定量PCR检测KCNKl6的表达水平。结果KCNKl6在大鼠胰岛中高表达。葡萄糖、催乳素和脂肪酸并不影响大鼠胰岛KCNKl6的表达。TSA显著增强大鼠胰岛葡萄糖和KCl刺激的胰岛素分泌（P〈0．05），同时显著下调KCNKl6的mRNA和蛋白表达（P〈0．01）。在INSl-E细胞，TSA抑制KCNKl6的表达作用呈浓度和时间依赖性（P〈0．05）。结论KCNKl6在大鼠胰岛中特异性高表达，且其表达水平能被TSA显著下调．KCNKl6表达的下调有可能介导了TSA增强的胰岛素分泌．Objective To observe the expression of a two-pore domain K＋ channel KCNK16 in rat islets, and to explore its regulation by insulin secretagogues. Methods Real time-PCR and immunohistoehemistry were employed to observe the expression of KCNK16 in rat islets and other tissues. Rat islets were exposed to glucose, prolactin, palmitate, and trichostatin A （TSA） for24 h and KCNK16 expression were determined by reahime-PCR and Western blot. Glucose- and KCl-stimulated insulin secretion were assayed by ELISA after islets were exposed to TSA for 24 h. The dose- and time-dependent effects of TSA on KCNK16 expression in INS1 -E cells were determined by RT- PCR. Results KCNK16 was highly expressed in rat islets. Glucose, prolactin, and palmitate did not affect the expression of KCNK16 in rat islets. TSA treatment significantly potentiated glucose- and KCl-stimulated insulin secretion in isolated rat islets （ P 〈 0.05 ）, along with decreased KCNK16 mRNA and protein expressions （ P 〈 O. 01 ）. TSA inhibited KCNK16 expression in a dose- and time-dependent manner in INS1-E cells （P 〈 0.05 ）. Conclusion KCNK16 is exclusively and highly expressed in rat islets and its expression can be down-regulated by TSA treatment. It is possible that TSA enhances insulin secretion via decreasing KCNK16 expression.

关 键 词：KCNK16 胰岛 胰岛素分泌 曲古霉素A 

分 类 号：R587.1[医药卫生—内分泌]