Liver-specific insulin resistance is associated with the development of the main challenges in metabolism, resulting in dyslipidemia, hyperinsulinemia and hyperglycemia. In vitro models developed for researching hepatic insulin resistance are limited and employed cell lines without similar characteristics to primary human hepatocytes. The Huh7 cell line has been established as a model with similar characteristics to primary human hepatocytes. In addition, it has been identified in the Huh7 cell line that infection with the hepatitis C virus induces insulin resistance. Therefore, we analyzed the induction of insulin resistance (IR) in the Huh7 cell line using an overdosage of insulin and treatment with metformin for its reversal, with the purpose of establishing an insulin resistance model useful for metabolic and pharmacological studies. Insulin-resistant Huh7 (Huh7-IR) showed a reduction in Glut2, glycogen levels, and glucose uptake stimulated by insulin or tyrosine phosphorylation from the β-fraction of insulin receptor post-insulin stimulation, with an increase of glucose production and lipid intracellular content. These biomarkers are frequently observed in insulin-resistant hepatic cells. Moreover, treatment of Huh7-IR with 0.5, 1 or 2 mM of metformin by 24 h decreased the biomarkers associated with an insulin-resistant state. These results suggest that Huh7-IR could be used as an in vitro system to research hepatic insulin resistance in metabolic and pharmacological studies.

中文翻译：

---

Huh7 细胞在诱导胰岛素抵抗和二甲双胍后处理后的表征。

肝脏特异性胰岛素抵抗与代谢主要挑战的发展相关，导致血脂异常、高胰岛素血症和高血糖。为研究肝胰岛素抵抗而开发的体外模型有限，并且使用的细胞系与原代人肝细胞没有相似的特征。Huh7细胞系已被建立为与原代人肝细胞具有相似特征的模型。此外，在Huh7细胞系中已发现丙型肝炎病毒感染会诱发胰岛素抵抗。因此，我们分析了使用过量胰岛素并用二甲双胍治疗逆转Huh7细胞系中胰岛素抵抗（IR）的诱导，目的是建立可用于代谢和药理学研究的胰岛素抵抗模型。胰岛素抵抗 Huh7 (Huh7-IR) 显示胰岛素刺激后 Glut2、糖原水平和葡萄糖摄取减少，或胰岛素刺激后胰岛素受体 β 部分的酪氨酸磷酸化，同时葡萄糖产生和细胞内脂质含量增加。这些生物标志物经常在胰岛素抵抗肝细胞中观察到。此外，用 0.5、1 或 2 mM 二甲双胍治疗 Huh7-IR 24 小时可降低与胰岛素抵抗状态相关的生物标志物。这些结果表明Huh7-IR可作为体外系统在代谢和药理学研究中研究肝胰岛素抵抗。