miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes.

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.

• Authors: Lin Dou, Ting Zhao, Lilin Wang, Xiuqing Huang, Juan Jiao, Dan Gao, Hangxiang Zhang, Tao Shen, Yong Man, Shu Wang, Jian Li
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 31 Pg. 22596-606 (Aug 02 2013) ISSN: 1083-351X [Electronic] United States
• PMID: 23798681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Interleukin-6
• MicroRNAs
• Mirn200 microRNA, mouse

Topics

• Animals
• Base Sequence
• DNA Primers
• Hepatocytes (metabolism)
• Insulin Resistance
• Interleukin-6 (physiology)
• Male
• Mice
• MicroRNAs (physiology)
• Polymerase Chain Reaction