Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2019 Sep 14;20(18):4569. doi: 10.3390/ijms20184569.
Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
胰岛素抵抗和糖尿病均与慢性丙型肝炎病毒（HCV）感染相关，胰高血糖素样肽-1（GLP-1）受体激动剂利拉鲁肽是治疗糖尿病的常用药物。我们旨在研究利拉鲁肽治疗是否能抑制 HCV 复制。通过将体外转录的 JFH-1 基因组 RNA 转染入 Huh-7.5 细胞，生成细胞培养产生的 HCV 感染性系统。提取总 RNA 样本以确定 HCV 复制的效率。用利拉鲁肽处理 Ava5 细胞并计算细胞活力。进行蛋白表达的 Western blot 分析。还检测了免疫反应性印迹信号。利拉鲁肽在 HCV 感染性系统中激活了 GLP-1 受体，并抑制了 HuH-7.5 细胞中的亚基因组 HCV RNA 复制。Western blot 分析表明，利拉鲁肽以剂量依赖性方式降低 HCV 蛋白和复制子 RNA 的表达。利拉鲁肽以 120μg/ml 的最佳浓度降低 HCV RNA 的细胞活力，激活 5'腺苷单磷酸激活蛋白激酶（AMPK）和磷酸化调节环腺苷单磷酸（CAMP）反应元件结合蛋白 2（TORC2），从而降低磷酸烯醇丙酮酸羧激酶（PEPCK）和 G6pase RNA 的细胞活力。因此，我们得出结论，利拉鲁肽可以通过 AMPK/TORC2 依赖的途径抑制 HCV 复制。
