同型半胱氨酸对葡萄糖代谢和骨骼肌p-Akt(Ser-473)的影响

Effect of Homocysteine on Glucose Metabolism and p-Akt (Ser-473) in Muscle Tissue

目的在高同型半胱氨酸血症中,探讨同型半胱氨酸对葡萄糖代谢和骨骼肌组织PI3K/Akt胰岛素信号通路中p-Akt(Ser-473)的影响,揭示同型半胱氨酸诱导葡萄糖代谢异常的机理.方法 40只小鼠随机分为空腹正常对照组、空腹高同型半胱氨酸血症组、进食正常对照组和进食高同型半胱氨酸血症组,每组10只;空腹高同型半胱氨酸血症组和进食高同型半胱氨酸血症组用含1.5%的甲硫氨酸饮水3个月.3个月后,各组取血分别测定同型半胱氨酸、葡萄糖、胰岛素,计算胰岛素敏感指数;利用Western blot检测p-Akt(Ser-473)的改变.结果空腹高同型半胱氨酸血症组与空腹正常对照组、进食高同型半胱氨酸血症组与进食正常对照组比较葡萄糖和胰岛素增加(P<0.05),胰岛素敏感指数降低(P<0.05),p-Akt(Ser-473)蛋白下调(P<0.05),Akt无明显变化.结论同型半胱氨酸可诱导葡萄糖代谢异常,这可能与骨骼肌组织PI3K/Akt胰岛素信号通路的p-Akt(Ser-473)降低有关.

Objective To discuss the effect of homocysteine on glucose metabolism and p-Akt（Ser-473） in the PI3K/Akt insulin signal pathway in the muscle tissues of mice with hyperhomocystienemia,and to reveal the mechanism of abnormal glucose metabolism induced by homocysteine.Methods Forty mice were divided into the fasting control group（n=10）,the feeding control group（n=10）,the fasting hyperhomocysteinemia（HHcy） group（n=10） and the feeding HHcy group（n=10）.Normal food and 1.5%（mass fraction） methionine were fed in the fasting HHcy group and the feeding HHcy group.After mice in each group were fed for three months,the blood was obtained.The blood glucose and blood insulin levels were detected.The insulin sensitivity index was calculated.Akt and p-Akt（Ser-473） were observed in the muscle tissue by the western blot.Results In the fasting HHcy group or the feeding HHcy group,the blood levels of glucose and insulin were higher than the fasting normal control group or the feeding normal control group（P0.05）,the insulin sensitivity index was decreased（P0.05）.Expression levels of p-Akt（Ser-473） were decreased compared the fasting normal control group or the feeding normal control group（P 0.05）.Expression levels of Akt had no obvious changes in each group. Conclusion Homocysteine induces abnormal glucose metabolism,the mechanism may be related with the decrease of the phosphorylation of Akt（Ser-473） in the PI3K/Akt insulin signal pathway in muscle tissue.