AMPK与肝脏糖异生研究进展

Research Progress of AMPK and Hepatic Glucolipid Metabolism

关键词:  腺苷酸活化蛋白激酶  肝脏糖脂代谢  糖异生  PEPCK  G6Pase  转录调节因子

Key words:  AMP activated protein kinase (AMPK)  hepatic glucolipid metabolism  gluconeogenesis  PEPCK  G6Pase  transcriptin regulators

摘要:

腺苷酸活化蛋白激酶（AMP activated protein kinase，AMPK）是一种广泛参与多种代谢调节的激酶，是主要的细胞“能量感受器”。AMPK通过α亚基的Thr172发生磷酸化而激活，通过抑制脂质合成相关转录因子以及肝脏糖异生来控制脂质合成以及血糖稳定。肝脏糖异生的调控过程中，通过激素及转录因子如FoxO1、CREB、TORC2、HNF-4α、PGC-1α等的参与，最后将信号传达至糖异生的2个关键性限速酶基因PECK与G6Pase，起到调控作用。激活的AMPK能抑制糖异生转录因子及相关关键酶的有效表达，阻止肝脏发生糖异生，进而下降血糖浓度。本文旨在讨论与总结AMPK在肝脏糖脂代谢中的作用，重点分析AMPK与肝脏糖异生信号通路转录因子之间的联系。

Abstract:

AMP activated protein kinase (AMPK) is a kind of kinase that widely involved in various metabolic regulation,which is the main cellular energy sensor.AMPK is activated by the Thr172 phosphorylation of alpha subunit,which can control lipid synthesis and glucose stability by the inhibition of the related transcription factor in lipid synthesis and hepatic gluconeogenesis.Liver gluconeogenesis is regulated by the hormone and crosstalks among transcription factors such as FOXO1,CREB,TORC2,HNF-4α,PGC-1α and eventually put the signal back to the two key enzyme genes PEPCK and G6Pase of gluconeogenesis.The activated AMPK can inhibit expression of key gluconeogenic enzymes and transcription factors,thereby inhibition of hepatic gluconeogenesis and reducing the blood glucose level.In this review,we aim to discuss and summarize the role of AMPK in liver glucolipid metabolism,focusing on the analysis of the link between AMPK and transcription factors of liver gluconeogenesis signaling.