Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion.
Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion.
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DOI：
10.1002/emmm.201200218
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发表时间：
2012-05
影响因子：
11.1
通讯作者：
Terlau, Heinrich
中科院分区：
文献类型：
--
作者：
Finol-Urdaneta, Rocio K.;Remedi, Maria S.;Raasch, Walter;Becker, Stefan;Clark, Robert B.;Struever, Nina;Pavlov, Evgeny;Nichols, Colin G.;French, Robert J.;Terlau, Heinrich
葡萄糖刺激的胰岛素分泌（GSIS）依赖于β细胞膜的重复性电尖峰活动。电压门控钾通道（Kv）的周期性激活产生一个外向的“延迟整流”钾电流，驱动每个尖峰的复极化阶段并调节胰岛素释放。虽然有几个KV通道在胰岛中表达，但它们对GSIS的贡献仍不完全清楚。我们利用天然存在的锥螺肽毒素，Conkunitzin-S1（Conk-S1），它选择性地阻断Kv1.7通道，提供一个内在的限制，精细分级控制总β细胞延迟整流电流，因此GSIS。Conk-S1可能通过减少β细胞中Kv1.7介导的延迟整流电流增加离体大鼠胰岛中的GSIS，从而增加动作电位放电和细胞质游离钙。在大鼠中，Conk-S1增加葡萄糖依赖性胰岛素分泌，而不降低基础葡萄糖。因此，我们得出结论，Kv1.7有助于在GSIS过程中β细胞的膜复极化电流，阻断β细胞Kv电流的这一特定组分提供了一种潜在的策略，用于增强GSIS，同时在代谢紊乱（如2型糖尿病）期间低血糖的风险最小。
Glucose-stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage-gated potassium channels (Kv) generates an outward, ‘delayed rectifier’ potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several Kv channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone-snail peptide toxin, Conkunitzin-S1 (Conk-S1), which selectively blocks Kv1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk-S1 increases GSIS in isolated rat islets, likely by reducing Kv1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that Kv1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell Kv current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.
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影响因子：
3.8
作者：
Finol-Urdaneta, Rocio K;Struver, Nina;Terlau, Heinrich
通讯作者：
Terlau, Heinrich
影响因子：
3.8
作者：
Horn, R;Marty, A
通讯作者：
Marty, A
影响因子：
5.5
作者：
Houamed, Khaled M.;Sweet, Ian R.;Satin, Leslie S.
通讯作者：
Satin, Leslie S.
影响因子：
1.6
作者：
Bayrhuber, Monika;Graf, Roland;Becker, Stefan
通讯作者：
Becker, Stefan
影响因子：
--
作者：
MacDonald, PE;Ha, XF;Wheeler, MB
通讯作者：
Wheeler, MB