AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase
AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase
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DOI：
10.1073/pnas.1119751109
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发表时间：
2012-01-10
影响因子：
11.1
通讯作者：
Kim, Sangwon F.
中科院分区：
文献类型：
--
作者：
Bang, Sookhee;Kim, Seyun;Kim, Sangwon F.
AMP激活的激酶（AMPK）感知细胞的能量状态并调节燃料可用性，而下丘脑AMPK调节食物摄入。我们报告说，肌醇多磷酸多激酶（IPMK）调节葡萄糖信号AMPK的途径，使葡萄糖激活磷酸化的IPMK在酪氨酸174使酶结合AMPK和调节其激活。因此，再喂养禁食小鼠迅速和显着刺激IPMK表达的转录增强，同时下调AMPK。此外，AMPK在下丘脑IPMK基因缺失的小鼠中上调。IPMK在生理上结合AMPK，葡萄糖处理增强了结合。葡萄糖对下丘脑细胞系中磷酸化AMPK的调节可通过阻断AMPK-IPMK结合来阻止。这些发现意味着IPMK抑制剂将有益于治疗肥胖和糖尿病。
he 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.