Horm Metab Res 2008; 40(1): 8-12
DOI: 10.1055/s-2007-1004515
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Long-term Interleukin-1α Treatment Inhibits Insulin Signaling via IL-6 Production and SOCS3 Expression in 3T3-L1 Adipocytes

T. Uno 1 , J. He 1 , I. Usui 1 , Y. Kanatani 1 , A. Bukhari 1 , S. Fujisaka 1 , Y. Yamazaki 1 , H. Suzuki 1 , M. Iwata 1 , M. Ishiki 1 , M. Urakaze 1 , T. Haruta 1 , H. Ogawa 1 , M. Kobayashi 1
  • 1First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
Further Information

Publication History

received 26.02.2007

accepted 09.07.2007

Publication Date:
17 December 2007 (online)


Proinflammatory cytokines are well-known to inhibit insulin signaling to result in insulin resistance. IL-1α is also one of the proinflammatory cytokines, but the mechanism of how IL-1α induces insulin resistance remains unclear. We have now examined the effects of IL-1α on insulin signaling in 3T3-L1 adipocytes. Prolonged IL-1α 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-1α treatment. Concomitantly, the level of IL-6 in the medium and STAT3 phosphorylation were increased by the prolonged IL-1α treatment. Addition of anti-IL-6 neutralizing antibody to the medium or overexpression of dominant-negative STAT3 decreased the IL-1α-stimulated STAT3 activation and SOCS3 induction, and ameliorated insulin signaling. These results suggest that the IL-1α-mediated deterioration of insulin signaling is largely due to the IL-6 production and SOCS3 induction in 3T3-L1 adipocytes.



I. Usui

First Department of Internal Medicine

Faculty of Medicine

University of Toyama

2630 Sugitani

930-0194 Toyama


Phone: +81/76/434 72 87

Fax: +81/76/434 50 25

Email: isaousui-tym@umin.ac.jp