Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their\neffects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma\n(HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced\ndiabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks.\nGlycemic control, hepatocarcinogenesis, and liver histology were compared between the groups.\nFasting blood glucose levels were significantly lower in the liraglutide group than in the control\ngroup (210.0 17.3 mg/dL vs. 601.8 123.6 mg/dL), and fasting insulin levels were significantly\nincreased by liraglutide (0.18 0.06 ng/mL vs. 0.09 0.03 ng/mL). Liraglutide completely suppressed\nhepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 3.87;\naverage tumor size, 8.1 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and\nhepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and\ninsulin-positive -cells were observed in the pancreas in liraglutide-treated mice but not in control\nmice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic\nmice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes.
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