幼年大鼠溺水应激后胰岛素信号传导变化及外源胰岛素治疗反应

Objective To explore the alteration of insulin signal transduction in drowning-induced stress hyperglycemia and to investigate therapeutic effect of insulin on it.Methods Stress hyperglycemia model was induced by drowning.Thirty-two infant rats were randomized into control,drowning,air resuscitation and air-insulin resuscitation groups.Insulin was injected abdominally into the air-insulin resuscitation rats.Fasting serum glucose and insulin were determined routinely,and protein expressions and serine phosphorylation levels of insulin receptor substrate 1(IRS-1) in muscle tissue were detected by Western blot and immunoprecipitation.The expressions of glucose transporter 4(GLUT4) in the intracellular and plasma membranes of muscle tissue were detected by Western blot.Results In the drowning group,insulin resistance index(HOMA-IR) increased significantly as compared with that of the control group,but the level of IRS-1 had no significantly change as compared with the other three groups.As compared with that of the drowning group(0.71±0.12),IRS-1 serine phosphorylation levels of the two resuscitation groups decreased significantly(0.56±0.13 and 0.46±0.08 respectively).The intracellular GLUT4 expression in the two resuscitation groups(1.82±0.11 and 1.96±0.28 respectively)increased significantly in contrast to that of the drowning group(1.45±0.15),and the air-insulin resuscitation groups showed an especially high increase of intracellular GLUT4 expression.Conclusion During the drowning-induced stress hyperglycemia,the alteration of serine phosphorylation and GLUT4 distribution is one of the important mechanism of insulin resistance.Insulin may decrease the blood glucose through decreasing serine phosphorylation levels of IRS-1 and increasing the intracellular GLUT4 expressions.

The alteration of insulin signal transduction in drowning-induced stress hyperglycemia Infant rats and the therapeutic effect of iusulin