K(ATP) channels and islet hormone secretion: new insights and controversies.
K(ATP) channels and islet hormone secretion: new insights and controversies.
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DOI：
10.1038/nrendo.2013.166
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Rorsman P
中科院分区：
文献类型：
--
作者：
Ashcroft FM;Rorsman P
三磷酸腺苷敏感钾通道(KATP通道)通过控制细胞膜电位将细胞代谢与电活动联系起来。它们参与许多生理过程，但通过调节胰岛细胞的激素分泌，在全身葡萄糖稳态中起着特别重要的作用。葡萄糖诱导的KATP通道关闭是胰岛素分泌的关键。新出现的数据表明，KATP通道在胰高血糖素的分泌中也起着关键作用，尽管它们到底是如何做到这一点仍然存在争议。这篇综述强调了KATP通道在胰岛素和胰升糖素分泌中的作用。我们讨论了KATP通道如何不仅有助于胰岛素释放的启动，而且还有助于随着葡萄糖浓度的增加而逐步刺激胰岛素的分泌。本文还对KATP通道在胰升糖素释放中作用的各种假说进行了综述。此外，我们还说明了KATP通道基因突变如何导致胰岛素分泌不足或分泌过多，如新生儿糖尿病和先天性高胰岛素血症，以及通道代谢调节缺陷可能是2型糖尿病特征的低胰岛素血症和高血糖素血症的基础。最后，我们概述了抑制KATP通道的磺脲类药物如何刺激新生儿糖尿病或2型糖尿病患者的胰岛素分泌，并提示它们可能用于靶向糖尿病中发现的胰升糖素分泌缺陷。
ATP-sensitive potassium channels (KATP channels) link cell metabolism to electrical activity by controlling the cell membrane potential. They participate in many physiological processes but have a particularly important role in systemic glucose homeostasis by regulating hormone secretion from pancreatic islet cells. Glucose-induced closure of KATP channels is crucial for insulin secretion. Emerging data suggest that KATP channels also play a key part in glucagon secretion, although precisely how they do so remains controversial. This Review highlights the role of KATP channels in insulin and glucagon secretion. We discuss how KATP channels might contribute not only to the initiation of insulin release but also to the graded stimulation of insulin secretion that occurs with increasing glucose concentrations. The various hypotheses concerning the role of KATP channels in glucagon release are also reviewed. Furthermore, we illustrate how mutations in KATP channel genes can cause hyposecretion or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, and how defective metabolic regulation of the channel may underlie the hypoinsulinaemia and the hyperglucagonaemia that characterize type 2 diabetes mellitus. Finally, we outline how sulphonylureas, which inhibit KATP channels, stimulate insulin secretion in patients with neonatal diabetes mellitus or type 2 diabetes mellitus, and suggest their potential use to target the glucagon secretory defects found in diabetes mellitus.
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