ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis

被引：419

作者：

Miki, T

Liss, B

Minami, K

Shiuchi, T

Saraya, A

Kashima, Y

Horiuchi, M

Ashcroft, F

Minokoshi, Y

Roeper, J

Seino, S ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan

[2] Univ Oxford, MRC, Anat Neuropharmacol Unit, Oxford OX1 3TH, England

[3] Ehime Univ, Sch Med, Dept Biochem Med, Matsuyama, Ehime 7910295, Japan

[4] Univ Oxford, Univ Lab Physiol, Oxford OX1 3TH, England

来源：

NATURE NEUROSCIENCE | 2001年 / 4卷 / 05期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/87455

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K-ATP channels in many cell types, including pancreatic beta -cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K-ATP) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2(-/-) mice. Although pancreatic alpha -cells were functional in Kir6.2(-/-), the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that K-ATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis.

引用

页码：507 / 512

页数：6

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[1] Molecular biology of adenosine triphosphate-sensitive potassium channels [J].