Akt磷酸化修饰在妊娠糖尿病线粒体氧化应激中的调控作用

Regulation of Akt phosphorylation in mitochondrial oxidative stress in gestational diabetes mellitus

妊娠糖尿病(GDM)是一种妊娠期常见并发症,其发病机制较为复杂,尚不明确。越来越多的证据表明线粒体氧化应激在GDM发生发展中起关键作用。蛋白激酶B(Akt)作为胰岛素信号通路中的一个关键节点,Akt活化后可引起Akt及其下游底物蛋白雷帕霉素靶蛋白(mTOR)、叉头转录因子O1(FOXO1)磷酸化级联反应,引发线粒体一系列的生物学效应来调控线粒体氧化应激与自噬水平,从而影响Akt磷酸化Akt160ku的底物(AS160)和磷脂酰肌醇4-磷酸5-激酶(PIP5K)表达,进而影响葡萄糖转运蛋白4(GLUT4)转运水平,最终对妊娠糖尿病病理改变产生重大影响。本文总结Akt磷酸化修饰在GDM线粒体氧化应激中的作用机制,以期为妊娠期并发症的防治提供新思路。

Gestational diabetes mellitus(GDM)is a common complication during pregnancy,and its pathogenesis is relatively complex and is still unclear.More a nd more evidence shows that mitochondrial oxidative stress plays a crucial role in the occurrence and development of GDM.Protein kinase B(Akt)is a key node in the insulin signaling pathway.The activation of Akt can lead to a phosphorylation cascade of Akt and its downstream substrate opaloprapamycin target protein(mTOR)and forks transcription factor O1(FOXO1),triggering a series of biological effects in mitochondria to regulate mitochondrial oxidative stress and autophagy levels,thereby affecting the expression of Akt phos phorylated Akt160ku substrate(AS160)and phos phatidylinositol 4-phosphate 5-kinase(PIP5K),which in turn affects the level of glucose transporter 4(GLUT4)transport,and ultimately has a significant impact on the pathological changes of gestational diabetes mellitus.In this paper,the mechanism of Akt phosphorylation modification in GDM mitochondrial oxidative stress is summarized,in order to provide new ideas for the prevention and treatment of pregnancy complications.