Roles of ATP-sensitive K+ channels as metabolic sensors -: Studies of Kir6.x null mice
Roles of ATP-sensitive K+ channels as metabolic sensors -: Studies of Kir6.x null mice
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DOI：
10.2337/diabetes.53.suppl_3.s176
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Seino, S
中科院分区：
文献类型：
--
作者：
Minami, K;Miki, T;Seino, S
ATP敏感性钾通道(K-ATP通道)存在于多种组织中，包括胰岛β细胞、心脏、骨骼肌、血管平滑肌和脑。K-ATP通道是由内向整流性K+通道(Kir6.x)和磺脲受体(SUR)亚基组成的异八聚体蛋白。Kir6.x和SuR亚基的不同组合构成了具有不同电生理和药理学特性的K-ATP通道。最近对基因工程小鼠的研究为包含Kir6.x的K-ATP通道的生理和病理生理学作用提供了洞察力。对Kir6.2基因缺失小鼠的分析表明，胰腺P细胞和下丘脑的Kir6.2/SUR1通道分别是葡萄糖诱导的胰岛素分泌和低血糖诱导的胰升糖素分泌所必需的，并且Kir6.2/SUR2通道参与骨骼肌对葡萄糖的摄取。脑内含Kir6.2的K-ATP通道也参与了对缺氧性全身性癫痫的保护作用。在心血管组织中，含有Kir6.1的K-ATP通道参与了血管张力的调节。此外，Kir6.1基因缺失的小鼠也是人类的一种金属心绞痛模型。我们对Kir6.2缺失和Kir6.1缺失小鼠的研究表明，K-ATP通道在急性代谢变化中是关键的代谢感受器，包括高血糖、低血糖、缺血和缺氧。
ATP-sensitive K+ channels (K-ATP channels) are present in various tissues, including pancreatic beta-cells, heart, skeletal muscles, vascular smooth muscles, and brain. K-ATP channels are hetero-octameric proteins composed of inwardly rectifying K+ channel (Kir6.x) and sulfonylurea receptor (SUR) subunits. Different combinations of Kir6.x and SUR subunits comprise K-ATP channels with distinct electrophysiological and pharmacological properties. Recent studies of genetically engineered mice have provided insight into the physiological and pathophysiological roles of Kir6.x-containing K-ATP channels. Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic P-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles. Kir6.2-containing K-ATP channels in brain also are involved in protection from hypoxia-induced generalized seizure. In cardiovascular tissues, Kir6.1-containing K-ATP channels are involved in regulation of vascular tonus. In addition, the Kir6.1 null mouse is a model of Prinzmetal angina in humans. Our studies of Kir6.2 null and Kir6.1 null mice reveal that K-ATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.