miR-200s Contribute to Interleukin-6 (IL-6)-induced Insulin Resistance in Hepatocytes

作者：Lin Dou, Ting Zhao, Lilin Wang, Xiuqing Huang, Juan Jiao, Dan Gao, Hangxiang Zhang, Tao Shen, Yong Man, Shu Wang, Li J · 发表于：Journal of Biological Chemistry · 年份：2013 · DOI：10.1074/jbc.m112.423145 · 被引用次数：67 · 研究领域：MicroRNA in disease regulation、RNA Research and Splicing、RNA modifications and cancer

By influencing the activity of the PI3K/AKT pathway, IL-6 acts as an important regulator of hepatic insulin resistance. miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. The present study showed that elevated serum concentration of IL-6 is associated with decreased levels of miR-200s, impaired activation of the AKT/glycogen synthase kinase (GSK) pathway, and reduced glycogenesis that occurred in the livers of db/db mice. As shown in the murine NCTC 1469 hepatocytes and the primary hepatocytes treated with 10 ng/ml IL-6 for 24 h and in 12-week-old male C57BL/6J mice injected with 16 μg/ml IL-6 by pumps for 7 days, IL-6 administration induced insulin resistance through down-regulation of miR-200s. Moreover, IL-6 treatment inhibited the phosphorylation of AKT and GSK and decreased the glycogenesis. The effects of IL-6 could be diminished by suppression of FOG2 expression. We concluded that IL-6 treatment may impair the activities of the PI3K/AKT/GSK pathway and inhibit the synthesis of glycogen, perhaps via down-regulating miR-200s while augmenting FOG2 expression. Background: miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. Results: IL-6 inhibited the phosphorylation of AKT and GSK through down-regulation of miR-200s. Conclusion: IL-6 may impair activation of the PI3K/AKT/...