小鼠肝脏ChREBP的表达与高胰岛素血症的实验研究

The hepatic ChREBP expression and hyperinsulinemia in mice

探讨血胰岛素水平对机体碳水化合物反应元件结合蛋白(ChREBP)及乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(FAS)表达的影响。分别应用高血胰岛素合并高血糖的KKAy小鼠模型和高血胰岛素DIO小鼠模型,采用Western blotting法观察动物肝脏ChREBP、FAS和ACC蛋白水平。结果显示,KKAy小鼠血胰岛素与血糖水平(r=0.902,P<0.000)、血胰岛素与血TG水平(r=0.732,P<0.000)均呈明显正相关;且随着血胰岛素水平的升高,其肝脏ChREBP、FAS和ACC的蛋白表达也呈渐进性升高。DIO小鼠血胰岛素与血糖水平无明显相关性;血胰岛素与血TG水平呈明显正相关(r=0.722,P<0.001);随着胰岛素水平的升高,肝脏ChREBP及其调控的FAS、ACC的蛋白表达呈渐进性升高。结果提示,在代谢综合征小鼠模型中,血胰岛素水平对肝脏ChREBP的表达具有正向调控作用,机体长期的高血胰岛素状态可能会引起ChREBP及其靶基因蛋白的过表达,从而导致机体的糖脂代谢紊乱。

To explore the effects of serum insulin on the expression of ChREBP, ACC and FAS in vivo, KKAy mice which were characterized with high levels of both serum insulin and glucose and DIO mice which were characterized with high serum insulin level alone were utilized, separately. The age-matched C57BL/6J mice fed with standard chow were used as normal control （Con）. Expressions of hepatic ChREBP, ACC and FAS were detected by Western blotting. As the results, in KKAy mice, a positive correlation between the levels of serum insulin and glucose （r=0.902, P〈0.000）, as well as between the levels of serum insulin and TG （r=0.732, P〈0.000）, was observed. Meanwhile, the expressions of hepatic ChREBP, ACC and FAS increased significantly and accompanied with its hyperinsulinemia and hyperglycemia, separately. In DIO mice, correlation between the levels of serum insulin and TG （r=0.722, P〈0.001） also showed positive, and the expressions of hepatic ChREBP, ACC and FAS increased significantly and also accompanied with its hyperinsulinemia. However, their blood glucose values were almost normal. These demonstrated that hyperinsulinemia may cause glycolipid metabolic disorders by up-regulating the expression of ChREBP in vivo.