·糖尿病基础研究·

　　【摘要】 目的 探讨Exenatide对肥胖大鼠肝脏糖异生基因表达的作用。 方法 雄性SD大鼠随机分为正常对照(NC)组，高脂饮食(HF)组和高脂用药(HF+Exe)组。实验结束时测定肝脏叉头蛋白转录因子(FOXO1)、磷酸烯醇式丙酮酸(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，机制可能为抑制肝脏糖异生基因的表达。

　　【关键词】Exenatide;糖异生;肥胖;糖脂代谢;大鼠

Role of exenatide in hepatic gluconeogenesis in the diet-induced obese rats HU Jia, FENG Wen-huan, YUAN Xue-wen, et al.Department of Endocrinology, Gulou Hospital Affiliated to Nanjing University, Nanjing 210008, China

Corresponding author: ZHU Da-long, E-mail: zdldr@gmail.com

　　【Abstract】 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 lowered, 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.

　　【Keywords】Exenatide; Gluconeogenesis; Obesity; Glucose lipid metabolism