Members of the Kv1 and Kv2 voltage-dependent K+ channel families regulate insulin secretion
Members of the Kv1 and Kv2 voltage-dependent K+ channel families regulate insulin secretion
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DOI：
10.1210/me.15.8.1423
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发表时间：
2001-08-01
影响因子：
--
通讯作者：
Wheeler, MB
中科院分区：
文献类型：
--
作者：
MacDonald, PE;Ha, XF;Wheeler, MB
在胰腺β细胞中，电压依赖性K+（Kv）通道是复极化、Ca 2+通道关闭和胰岛素分泌限制的潜在介导物。β细胞中表达的特异性Kv通道及其对延迟整流电流和这些细胞中胰岛素分泌调节的贡献尚不清楚。在大鼠胰岛和胰岛素瘤细胞中检测到Kv1.4、1.6和2.1的高水平蛋白表达和mRNA转录。用四乙基铵抑制这些通道可使I-DR降低约85%，并使葡萄糖刺激的胰岛素分泌增加2至4倍。腺病毒介导的C-末端截短的Kv2.1亚基的表达，特异性地消除Kv 2家族电流，使这些细胞中的延迟整流电流减少60-70%，并使大鼠胰岛的葡萄糖刺激的胰岛素分泌增加60%。C-末端截短的Kv1.4亚基的表达，废除Kv 1通道家族电流，减少延迟整流电流约25%，提高葡萄糖刺激的大鼠胰岛胰岛素分泌40%。本研究确定Kv 2和I通道同源物。介导大部分大鼠β细胞的复极化延迟整流电流。Kv2.1的拮抗作用可能被证明是2型糖尿病的一种新的葡萄糖依赖性治疗。
In pancreatic beta -cells, voltage-dependent K+ (Kv) channels are potential mediators of repolarization, closure of Ca2+ channels, and limitation of insulin secretion. The specific Kv channels expressed in beta -cells and their contribution to the delayed rectifier current and regulation of insulin secretion in these cells are unclear. High-level protein expression and mRNA transcripts for Kv1.4, 1.6, and 2.1 were detected in rat islets and insulinoma cells. Inhibition of these channels with tetraethylammonium decreased I-DR by approximately 85% and enhanced glucose-stimulated insulin secretion by 2- to 4-fold. Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit, specifically eliminating Kv2 family currents, reduced delayed rectifier currents in these cells by 60-70% and enhanced glucose-stimulated insulin secretion from rat islets by 60%. Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40%. This study establishes that Kv2 and I channel homologs. mediate the majority of repolarizing delayed rectifier current in rat beta -cells. and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes.