腺苷酸活化蛋白激酶受肌醇多磷酸激酶的生理调节。
AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase.
机构信息
Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):616-20. doi: 10.1073/pnas.1119751109. Epub 2011 Dec 27.
Abstract
The AMP-activated kinase (AMPK) senses the energy status of cells and regulates fuel availability, whereas hypothalamic AMPK regulates food intake. We report that inositol polyphosphate multikinase (IPMK) regulates glucose signaling to AMPK in a pathway whereby glucose activates phosphorylation of IPMK at tyrosine 174 enabling the enzyme to bind to AMPK and regulate its activation. Thus, refeeding fasted mice rapidly and markedly stimulates transcriptional enhancement of IPMK expression while down-regulating AMPK. Also, AMPK is up-regulated in mice with genetic depletion of hypothalamic IPMK. IPMK physiologically binds AMPK, with binding enhanced by glucose treatment. Regulation by glucose of phospho-AMPK in hypothalamic cell lines is prevented by blocking AMPK-IPMK binding. These findings imply that IPMK inhibitors will be beneficial in treating obesity and diabetes.
摘要
腺苷酸活化蛋白激酶（AMPK）感知细胞的能量状态并调节燃料供应，而下丘脑 AMPK 则调节食物摄入。我们报告称，肌醇多磷酸激酶（IPMK）通过一种途径调节葡萄糖信号向 AMPK 的传递，在该途径中，葡萄糖激活 IPMK 酪氨酸 174 的磷酸化，使该酶能够与 AMPK 结合并调节其激活。因此，重新喂养禁食的小鼠会迅速而显著地刺激 IPMK 表达的转录增强，同时下调 AMPK。此外，下丘脑 IPMK 基因缺失的小鼠中 AMPK 上调。IPMK 与 AMPK 在生理上结合，葡萄糖处理增强结合。通过阻断 AMPK-IPMK 结合，可防止葡萄糖调节下丘脑细胞系中磷酸化 AMPK。这些发现表明，IPMK 抑制剂将有益于肥胖和糖尿病的治疗。
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