Mechanism Of Insulin Resistance Induced By PI3K Pathway

Insulin resistance(IR)is one of the main pathogenesis of type 2 diabetes mellitus(T2DM)and is widely found in many metabolic diseases,such as obesity,polycystic ovary syndrome(PCOS),non-alcoholic fatty liver(NAFLD),hyperlipidemia and hypertension.An epidemiological study found that IR was present in 80% of patients with T2DM.IR formation is closely related to abnormal insulin signaling pathway.For the insulin signaling pathway PI3K/Akt/GSK-3,IR can be triggered by any obstacle in the pre-receptor,in-receptor or post-receptor links.Postreceptor abnormality is the main mechanism of impaired insulin signaling pathway.The post-receptor abnormalities mainly include:(1)abnormal phosphorylation of insulin receptor substrate(IRS-1);The activation of phosphatidylinositol3 kinase(PI3K)was abnormal;(3)abnormal phosphoinositol-dependent protein kinase(PKD)and protein kinase(Akt);(4)glycogen synthase kinase-3(GSK-3)phosphorylation disorder;(5)glucose transporter 4(GLUT-4)synthesis and translocation obstacle.Abnormal post-receptor insulin signaling was associated with inflammatory factors such as tumor necrosis factor,TNF-a,c-reactive protein(CRP),interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and adiponectin(APN),leptin,and resistin.High plasma free fatty acid(FFA),mammalian target of rapamycin(mTOR),silencing information regulator(SIRT1)and other nutritional receptors were also involved.These factors inhibit IRS tyrosine phosphorylation,thereby blocking insulin signaling,which in turn leads to IR,leading to impaired glucose and lipid metabolism.This paper will make a comprehensive summary of the mechanisms by which inflammatory cytokines,adipocytokines,FFA,mTOR and SIRT1 cause abnormal insulin signaling pathways.