Exenatide对肥胖大鼠肝脏糖异生基因表达的观察

摘要

Objective To investigate the effect of exenatide on hepatic gluconeogenesis gene expression in diet-induced obese rats.Methods Male Sprague-Dawley rats were randomized into normal control (NC),high-fat diet (HF),and high-fat diet + exenatide (HF+Exe) groups.The mRNA expressions of Forkhead box1 (FoxO1),glucose-6-phosphatase (G6pase),and phosphoenolpyruvate carboxykinase (PEPCK) were measured.And the FoxO1 level in hepatic tissues was determined.Results The levels of FIns,TG,and FFA were elevated,the mRNA expressions of FoxO1,PEPCK,and G6Pase were up-regulated,and the level of FoxO1 was increased in the HF group compared with the NC group (P＜0.05).Eight weeks after treatment with exenatide,the levels of FIns,TG,TC,and FFA were lower,the mRNA expressions of FoxO1,PEPCK,and G6Pase were down-regulated,and the level of FoxO1 was decreased in the HF+Exe group compared with the NC group (P＜0.05).Conclusion Exenatide treatment could improve the hepatic glucose lipid metabolism,the underlying mechanism lies probably in the inhibition of hepatic gluconeogenesis gene expressions.%目的 探讨Exenatide对肥胖大鼠肝脏糖异生基因表达的作用. 方法 将雄性SD大鼠随机分为高脂饮食(HF)组、高脂用药(HF+ Exe)组与正常对照(NC)组.测定各组肝脏叉头蛋白转录因子O1(FoxO1)、磷酸烯醇式丙酮酸羧化酸(PEPCK)、葡萄糖-6-磷酸酶(G6Pase) mRNA,以及FoxO1蛋白水平. 结果 HF组FIns、TG、FFA升高,FoxO1、PEPCK、G6Pase mRNA表达上调,FoxO1蛋白水平增加(P＜0.05)；Exenatide用药8周后,HF+ Exe组FIns、TG、TC、FFA降低,FoxO1、PEPCK、G6Pase mRNA表达下调,FoxO1蛋白水平降低(P＜0.05). 结论 Exenatide具有改善肥胖大鼠糖脂代谢的作用,其机制可能为抑制肝脏糖异生基因的表达.