间歇低氧对大鼠胰岛素抵抗及骨骼肌细胞GLUT4、Akt2的影响

目的 检测不同间歇低氧暴露时间对骨骼肌葡萄糖转运蛋白(GLUT)4与蛋白激酶B(PKB/Akt)2表达的影响,探讨二者在间歇低氧导致胰岛素抵抗中的作用.方法 选取健康雄性Sprague-Dawley大鼠40只,按照随机数字表法分为5组:常氧对照组(NC组),间歇低氧2周组(IH2组),间歇低氧4周组(IH4组),间歇低氧6周组(IH6组),间歇低氧8周组(IH8组),每组8只.IH2组、IH4组、IH6组、IH8组每天给予8h间歇低氧暴露(9:00～17:00),NC组室内环境正常饲养.检测各组空腹血糖和空腹胰岛素水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR).采用免疫组织化学法检测大鼠骨骼肌GLUT4及Akt2蛋白的表达,蛋白表达量用平均灰度值表示,并分析GLUT4与Akt2的相关性.结果 与NC组相比,IH2组、IH4组、IH6组、IH8组空腹血糖、HOMA-IR升高,骨骼肌GLUT4与Akt2灰度值升高,并且随间歇低氧暴露时间的延长而升高明显(F =87.67～288.63,P均＜0.05);与NC组相比,IH2组、IH4组、IH6组、IH8组空腹胰岛素升高,其中IH2组、IH4组、IH6组,随间歇低氧暴露时间的延长而升高明显,IH8组较IH6组下降(F=86.04,P＜0.01).Pearson相关分析显示GLUT4与Akt2的表达呈正相关(r=0.895,P ＜0.05).结论 随着间歇低氧暴露时间的延长胰岛素抵抗程度增加,GLUT4与Akt2蛋白表达水平下降,二者在间歇低氧导致胰岛素抵抗的过程中起协同作用.

Effects of intermittent hypoxia on insulin resistance and expression of GLUT4 and Akt2 in skeletal muscle cells of rats

Objective To investigate the effects of different time of exposure to intermittent hypoxia on the expression of glucose transporter (GLUT) 4 and protein kinase B(PKB/Akt)2,and their roles in insulin resistance induced by intermittent hypoxia.Methods Forty male Sprauge-Dawley rats were divided into 5 groups by random number table method:normal control group (NC group),group of intermittent hypoxia for 2 weeks (IH2 group),group of intermittent hypoxia for 4 weeks (IH4 group),group of intermittent hypoxia for 6 weeks (IH6 group) and group of intermittent hypoxia for 8 weeks(IH8 group),with 8 rats in each group.Rats in IH2 group,IH4 group,IH6 group and IH8 group were exposed to intermittent hypoxia each day,from 9 a.m.to 5 p.m.,while rats in NC group were exposed to room air.Fasting blood glucose and fasting blood insulin were measured,and homeostatic model assessment of insulin resistance index(HOMA-IR) was calculated.The expression of GLUT4 and Akt2 protein in muscles of rat were analyzed by immunohistochemistry and quantified by the average gray value.The correlation between GLUT4 and Akt2 was analyzed.Results Compared with NC group,fasting blood glucose,HOMA-IR,GLUT4 and Akt2 in IH2,IH4,IH6,IH8 group were higher,and were increased with the exposure time of intermittent hypoxia (F =87.67-288.63,all P ＜ 0.05).Compared with NC group,fasting insulin was elevated in IH2,IH4,IH6 and IH8 group,and was increased along with the duration of intermittent hypoxia and then decreased in IH8 group(F =86.04,P ＜ 0.01).Pearson correlation analysis showed that the expression of GLUT4 was positively correlated with Akt2 (r =0.895,P ＜ 0.05).Conclusion The degree of insulin resistance increases and the expression of GLUT4 and Akt2 decrease with duration of intermittent hypoxia.GLUT4 and Akt2 play synergistic effects in insulin resistance induced by intermittent hypoxia.