Effects Of Hepatic Ischemia Reperfusion Injury On Insulin Signal Transduction In Rat Liver

Objective To observe the changes of insulin signal protein expression in rat liver after hepatic ischemia reperfusion injury.Methods A total of 80 healthy Sprague Dawley rats were divided randomly into ischemia-reperfusion group(I/R)and control group(C) with 40 rats in each.In I/R group,the hepatic ischemia reperfusion injury(HIRI)rat model was established(Hepatic ischemia was produced by clamping hepatic hilum for 30 min and reperfusion was allowed for 2h after release of the clamp).Blood samples were obtained before hepatic ischemia(T₁)and after reperfusion(T₂)to determine the levels of plasma glucose and insulin.Liver tissue were used to measure expression of insulin signal proteins such as insulin receptorβunit(IRβ),insulin receptor substrate-2(IRS-2)and p85 subunit of phosphatidylinositol 3-kinase(p85),and the levels of phosphotyrosine state of IRβ,IRS-2 and the interaction between IRS-2 and PI3K.Results The levels of plasma glucose in two groups were higher at T₂ than those at T₁(P＜0.01),but the increment in I/R group was more obvious(P＜0.01).Insulin concentrations in the I/R group did not vary significantly during T₁ and T₂.The level of insulin in C group at T₂ was higher than that at T₁(P＜0.05).The index of insulin resistance (HOMA-IR)in two groups were higher at T₂ than those at T₁(P＜0.01). The index of insulin secretion(IS)in I/R group at T₂ was less than that at T₁.Compared with those in C group,total protein expression of IRβ, IRS-2 and p85 in I/R group did not vary significantly;Compared with those in group C,tyrosine phosphorylation of IRβ,IRS-2 and the interaction between IRS-2 and PI3K at T₂ in the liver decreased by 32.2%(P＜0.01),47.7%(P＜0.01)and 55.6%(P＜0.01),respectivelyConclusion Hepatic ischemia-reperfusion inhibits insulin secretion and causes the expression of the phosphotyrosine state of insulin signal transducting proteins such as IRβ,IRS-2 and the interaction between IRS-2 and PI3K to decrease,so as to influence the glucose metabolism course.It is maybe one of the reasons for the elevation of plasma glucose after HIRI.