KATP channels and insulin secretion:: a key role in health and disease
KATP channels and insulin secretion:: a key role in health and disease
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DOI：
10.1042/bst0340243
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Ashcroft, FM
中科院分区：
文献类型：
--
作者：
Ashcroft, FM
本文综述了近5年来对胰岛β细胞三磷酸腺苷敏感钾通道结构和功能的研究进展。它讨论了最近对八聚体K-ATP通道复合体的结构研究以及核苷酸对KATP通道活性调节的研究。然后，它考虑了K-ATP通道Kir6.2亚单位的功能获得突变减少ATP对通道的抑制从而导致新生儿糖尿病的分子机制，以及这些突变的识别如何导致治疗的变化。最后，它以C57BL/6J小鼠为例，说明了葡萄糖耐量异常或糖尿病的小鼠模型如何为β细胞功能提供新的见解，C57BL/6J小鼠的葡萄糖耐量异常是由烟酰胺核苷酸转氢酶突变引起的。
This review summarizes advances in our understanding of the structure and function of the ATP-sensitive potassium (K-ATP) channel of the pancreatic beta-cell that have been made over the last 5 years. it discusses recent structural studies of the octameric K-ATP, channel complex and studies of the regulation of KATP channel activity by nucleotides. it then considers the molecular mechanism by which gain-of-function mutations in the Kir6.2 subunit of the K-ATP channel reduce channel inhibition by ATP and thereby lead to neonatal diabetes, and how identification of these mutations has led to changes in therapy. Finally, it illustrates how mouse models of glucose intolerance or diabetes can provide fresh insight into beta-cell function, using the C57BL/6J mouse, whose glucose intolerance arises from mutations in nicotinamide nucleotide transhydrogenase, as an example.