CAJ | 학술논문

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.
목적 탐토닉수응격대서적이도소신호전도변화급외원이도소치료반응.방법 채용닉수적방법건립응격성고혈당동물모형,32지유년대서수궤분위대조조、닉수질식조、공기복소조、공기복소연합이도소치료조.공기복소연합이도소치료조재복소시주사이도소.재닉수병복소과정중측정대서혈당、이도소、골격기이도소수체저물1(IRS-1)급기사안산린산화수평,검측골격기내외막적포도당전운체4(GLUT4)단백함량.결과 닉수조이도소저항지수승고,산생엄중적이도소저항,IRS-1함량무현저개변;공기복소조여공기복소연합이도소치료조적IRS-1사안산린산화수평(분별위0.56±0.13、0.46±0.08)균저우닉수질식조(0.71±0.12),차이유현저성(P＜0.05);외막적GLUT4단백함량(분별위1.82±0.11、1.96±0.28)현저고우닉수질식조(1.45±0.15),우이공기복소연합이도소치료조적변화경위현저.결론 재닉수질식도치적응격성고혈당과정중,IRS-1사안산린산화、GLUT4표체이상시이도소저항적중요조공점지일.이도소능개선IRS-1사안산린산화급GLUT4내외막분포,체도강저혈당적작용.
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.