miR-200s Contribute to Interleukin-6 (IL-6)-induced Insulin Resistance in Hepatocytes |
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Authors: | Lin Dou Ting Zhao Lilin Wang Xiuqing Huang Juan Jiao Dan Gao Hangxiang Zhang Tao Shen Yong Man Shu Wang Jian Li |
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Affiliation: | From the ‡Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China and ;the §Key Laboratory of Geriatrics, Beijing Institute of Geriatrics and Beijing Hospital, Ministry of Health, Beijing 100730, China |
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Abstract: | 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. |
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Keywords: | AKT Glycogen Glycogen Synthase Kinase 3 Interleukin MicroRNA |
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