Effects Of Hepatic Ischemia Reperfusion Injury On Insulin Signaling PI3K Pathway In Rat Skeletal Muscles

Effects of hepatic ischemia reperfusion injury on insulin signaling PI3K pathway in rat skeletal musclesObjective To investigate the effects of hepatic ischemia reperfusion injury on insulin signaling PI3K pathway in rat skeletal muscles.Methods Eighty healthy Sprague-Dawley rats were randomly divided into I/R group(I/R)and control group(C)with 40 rats each.Five milliliter inferior vena cava blood samples of ten rats in each group were drawn at 5 minutes before hepatic ischemia(T₁)and 2 hours after liver ischemia-reperfusion(T₂).These blood samples were used for determining the levels of glucose,insulin and glucagon.Skeletal muscles were used to measure the protein levels of insulin receptorβ-subunit(IR-β),insulin receptor substrate(IRS-1)and p85 subunit of phosphatidylinositol 3-kinase(PI3K).The phosphotyrosine state of IR-β, IRS-1 and p85 subunit of phosphatidylinositol 3-kinase(P85)in skeletal muscle were also determined with immune precipitation.Results In C group,the concentration of plasma glucose,glucagon and insulin elevated significantly at T₂ than those at T₁.Compared with those at T₁,the concentration of plasma glucose and glucagon in I/R group increased obviously at T2(p＜0.05),but the increment in I/R group was more obvious than those in C group(P＜0.01).The concentration of plasma insulin in I/R group did not vary significantly at T₂ compared with those at T₁.There were no significant changes in protein levels of IR-β, IRS-1 and p85 between two groups.Tyrosine phosphorylation of IRβ, IRS-1,and the interaction between IRS-1 and PI3K at T₂ in the skeletal muscles were decreased by 79%(P＜0.01),49%(P＜0.05)and 38% (P＜0.05)respectively.Conclusion Hepatic ischemia-reperfusion inhibits insulin secretion and induces insulin resistance via down-regulation of the early steps in insulin-signaling PI3K pathway in rats.