Therapeutic effect of metformin on type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease in rats / 中国医师杂志

ABSTRACT

ObjectiveTo investigate the therapeutic effect of mefformin on type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD).MethodsThe model rats of T2DM complicated with NAFLD were established by feeding high-glucose and high-fat diet, and injection of low dose streptozotocin.The model rats were randomly divided into 2 groups, model group (n = 16) and metformin group (n = 16).Twenty normal rats were set for normal control group.Intragastric administration lasted for 12 weeks.At the end of 16th week (after treated 8 weeks) and 20th week (after treated 12weeks), the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), fasting blood glucose (FBG),fasting insulin (FINs), triglyceride (TG), total cholesterol (TC) and free fatty acid (FFA) in each group were determined and the level of insulin sensitivity index (ISI) was determined.Meanwhile, pathological changes of liver, the expression of uncoupling protein-2 (UCP-2) mRNA and UCP-2 protein of liver tissues in each group were detected.ResultsThe levels of serum ALT, AST, FBG,FINs, serum TG , TC and FFA were significantly higher and ISI was significantly lower and the expression of UCP-2 protein significantly increased in model group, compared with control group (all P ＜ 0.01).The expression of UCP-2 mRNA at 16th and 20th week in model group were significantly higher than that in control group [(1.789 +0.301) vs (0.245 ±0.087), t =11.02, P ＜0.01 and (1.989 +0.207) vs (0.262+ 0.058), t = 17.93, P ＜ 0.01, respectively].Fatty degeneration of liver tissues was significantly exacerbated in model group.After treatment for 8 weeks and 12 weeks with mefformin, the levels of serum ALT,AST, FBG, serum TG, TC and FFA significantly decreased, ISI significantly increased, fatty degeneration of liver tissues was significantly improved, and the expression of UCP-2 protein significantly decreased,compared with model rats (P ＜ 0.01 or P ＜ 0.05).The expression of UCP-2 mRNA at 16th and 20th week in metformin group were significantly lower than that in model group [(0.665 + 0.088) vs (1.789 ±0.301), t = 7.81, P ＜ 0.01 and (0.610 ± 0.1 02) vs (1.989 ± 0.207), t = 9.98, P ＜ 0.01, respectivelv].ConclusionsMetformin has therapeutic effect on T2DM complicated with NAFLD.