Long-term interleukin-1 alpha treatment inhibits insulin signaling via IL-6 production and SOCS3 expression in 3T3-L1 adipocytes

作者：Uno T; He J; Usui I^*; Kanatani Y; Bukhari A; Fujisaka S; Yamazaki Y; Suzuki H; Iwata M; Ishiki M; Urakaze M; Haruta T; Ogawa H; Kobayashi M

来源：Hormone and Metabolic Research, 2008, 40(1): 8-12.

DOI：10.1055/s-2007-1004515

• interleukin-1 alpha
• insulin resistance
• IRS-1
• SOCS3
• IL-6

Proinflammatory cytokines are well-known to inhibit insulin signaling to result in insulin resistance. IL-1 alpha is also one of the proinflammatory cytokines, but the mechanism of how IL-1 alpha induces insulin resistance remains unclear. We have now examined the effects of IL-1 alpha on insulin signaling in 3T3-L1 adipocytes. Prolonged IL-1 alpha treatment for 12 to 24 hours partially decreased the protein levels as well as the insulin-stimulated tyrosine phosphorylation of IRS-1 and Akt phosphorylation. mRNA for SOCS3, an endogenous inhibitor of insulin signaling, was dramatically augmented 4 hours after IL-1 alpha a treatment. Concomitantly, the level of IL-6 in the medium and STAT3 phosphorylation were increased by the prolonged IL-1 alpha treatment. Addition of anti-IL-6 neutralizing antibody to the medium or overexpression of dominant-negative STAT3 decreased the IL-1 alpha-stimulated STAT3 activation and SOCS3 induction, and ameliorated insulin signaling. These results suggest that the IL-1 alpha-mediated deterioration of insulin signaling is largely due to the IL-6 production and SOCS3 induction in 3T3-L1 adipocytes.

• 出版日期2008-1