过氧化物酶增殖体激活受体-γ辅助激活因子1在OLETF大鼠肝脏糖代谢中的作用

The role of peroxisome proliferator-activated receptor-γ coactivator-1 in glucose metabolism in the liver of OLETF rat

目的:通过观察OLETF大鼠肝脏组织过氧化物酶增殖体激活受体-γ辅助激活因子1(PGC-1)表达的变化,初步探讨其在2型糖尿病肝糖代谢中的作用。方法:OLETF大鼠为实验组,同龄LETO大鼠为对照。在8、18和28周龄行OGTT试验,测血糖、胰岛素和血脂,Western blot方法测定肝组织中PGC-1、PEPCK、UCP2的蛋白水平。结果:(1)OLETF大鼠从8周起体重明显高于对照组,18、28周龄时OGTT 2h BG和TG水平均明显升高,28周龄时空腹胰岛素水平升高,胰岛素敏感指数降低。(2)OLETF大鼠肝脏组织中PGC-1蛋白表达18、28周时低于对照组,28周时PEPCK表达高于对照组,而UCP2表达低于对照,差异有统计学意义。结论:OLETF18周龄后表现出2型糖尿病病理特点,OLETF大鼠肝脏PGC-1、PEPCK及UCP2蛋白表达水平的变化,提示PGC-1可能在2型糖尿病的肝糖代谢中起重要作用。

Objective To investigate the effect of PGC-1 on hepatic glucose metabolism of type 2 diabetes by observing its changes in the liver of OLETF rats. Methods OLETF rats were observed, even-aged LETO rats were controled. Oral glucose tolerance test, Fasting Insulin, triglyceride and total cholesterol were measured and then the protein level of PGC-1, phosphoenolpyruvate earboxykinase and uncoupling protein 2 of liver tissue were detected by Western blot respectively in 8,18 and 28 weeks. Results （1）OLETF rats had significantly higher levels than LETO rats, in body weight, OGTT2h blood glucose and TG at 18th, 28th week. The levels of Fasting Insulin of OLETF rats were higher while insulin sensitive index were lower than that of LETO rats at 28th week. （2）Protein expressions in the livers： PGC-1 of OLETF rats was lower than that of LETO rats at 18th and 28th week. PEPCK of OLETF rats was more while UCP2 was lower than that of LETO rats at 28th week. Conclusions OLETF rats showed pathological phenotypes of type 2 diabetes. The changes of PGC-1, PEPCK and UCP2 in 28-weeks OLETF rat suggested that PGC-1 plays an important role in the liver glycometabolism in type 2 diabetes.