The study of the role of IRS1 and its serine phosphorylation activity in pathogenesis of insulin resistance

Objective To investigate the effects of insulin receptor substrate 1(IRS1) and activity of IRS1 serine phosphorylation on the development of insulin resistant. Methods 20 male C57BL/6 mice were divided into normal diet group(NC) and high fat diet group(HF) and all mice showed insulin resistance.The mice in HF were fed with high fat diet for 16 weeks.Serum insulin concentration was also evaluated by ELISA.RT-PCR,Western blot and immunofluorescence were performed to detect TSC2 and IRS1 mRNA and protein expression in skeletal muscle. Results As compared with NC group,HF group showed that fasting insulin value was increased(P0.01),OGTT was damaged,mRNA and protein expressions of TSC2 of skeletal muscle of mice were decreased(P0.05),and the expression of pIRS1Ser307 and pIRS1Ser636/639 was increased(P0.01).Conclusions High-fat diet possibly produces IR by inhibiting TSC2 mRNA and protein expression,and by increasing IRS1Ser307 and IRS1Ser636/639 phosphorylation levels in mice skeletal muscle.