AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase

作者：Bang Sookhee; Kim Seyun; Dailey Megan J; Chen Yong; Moran Timothy H; Snyder Solomon H; Kim Sangwon F^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(2): 616-620.

DOI：10.1073/pnas.1119751109

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.

• 出版日期2012-1-10