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

目的 探讨溺水应激大鼠的胰岛素信号转导变化及外源胰岛素治疗反应.方法 采用溺水的方法建立应激性高血糖动物模型,32只幼年大鼠随机分为对照组、溺水窒息组、空气复苏组、空气复苏联合胰岛素治疗组.空气复苏联合胰岛素治疗组在复苏时注射胰岛素.在溺水并复苏过程中测定大鼠血糖、胰岛素、骨骼肌胰岛素受体底物1(IRS-1)及其丝氨酸磷酸化水平,检测骨骼肌内外膜的葡萄糖转运体4(GLUT4)蛋白含量.结果 溺水组胰岛素抵抗指数升高,产生严重的胰岛素抵抗,IRS-1含量无显著改变;空气复苏组与空气复苏联合胰岛素治疗组的IRS-1丝氨酸磷酸化水平(分别为0.56±0.13、0.46±0.08)均低于溺水窒息组(0.71±0.12),差异有显著性(P＜0.05);外膜的GLUT4蛋白含量(分别为1.82±0.11、1.96±0.28)显著高于溺水窒息组(1.45±0.15),尤以空气复苏联合胰岛素治疗组的变化更为显著.结论 在溺水窒息导致的应激性高血糖过程中,IRS-1丝氨酸磷酸化、GLUT4表达异常是胰岛素抵抗的重要调控点之一.胰岛素能改善IRS-1丝氨酸磷酸化及GLUT4内外膜分布,达到降低血糖的作用.

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

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.