利拉鲁肽可能通过AMPK通路减轻2型糖尿病合并非酒精性脂肪肝小鼠的脂质代谢

Liraglutide May Reduce Lipid Metabolism in Mice with Type 2 Diabetes and Non-alcoholic Fatty Liver through AMPK Pathway

目的探究利拉鲁肽对2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)小鼠血糖和脂肪代谢的影响以及利拉鲁肽调控该过程中是否有AMPK信号通路的参与。方法KK/upj-ay/J小鼠(以下简称为KKay小鼠)随机分为普通饮食20只,高脂饮食40只,连续饲养4周,4周后每周检测血糖水平,确定造模是否成功。高脂饮食小鼠随机分为两组,一组利拉鲁肽,一组未治疗。尾静脉采少量血,进行血糖测定。空腹过夜后,左心室穿刺采集血样,检测总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。蛋白质印迹分析AMPK的磷酸化修饰是否改变。结果利拉鲁肽改善了KKay糖尿病脂肪小鼠的血糖和血脂水平,AMPK信号通路可能参与利拉鲁肽调节的脂质代谢和血糖改变。结论利拉鲁肽可能通过AMPK通路减轻T2DM合并NAFLD小鼠的代谢,为临床治疗T2DM合并NAFLD提供更多理论依据。

Objective To explore the effect of liraglutide on blood glucose and fat metabolism in type 2 diabetic mice with non-alcoholic fatty liver and whether liraglutide is involved in the AMPK signaling pathway during the regulation of this process.Methods KK/upj-ay/J mice(hereinafter referred to as KKay mice)were randomly divided into 20 normal diets and 40 high-fat diets.They were reared for 4 weeks.After 4 weeks,blood glucose levels were measured every week to determine if the model succeeded.High-fat diet mice were randomly divided into two groups,one group with liraglutide and one group untreated.A small amount of blood was collected from the tail vein for blood glucose measurement.After an overnight fasting,blood samples were collected by left ventricular puncture to detect total cholesterol,triacylglycerol,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol.Western blot analysis whether the phosphorylation modification of AMPK was changed.Results Liraglutide improved the blood glucose and blood lipid levels of KKay diabetic fat mice.AMPK signaling pathway may be involved in the lipid metabolism and blood glucose changes regulated by liraglutide.Conclusion Liraglutide may reduce the metabolism of type 2 diabetes with non-alcoholic fatty liver in mice through AMPK pathway,and provide more theoretical basis for clinical treatment of type 2 diabetes with non-alcoholic fatty liver.