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Journal of Endocrinological Investigation

, Volume 35, Issue 1, pp 28–34 | Cite as

Rosiglitazone attenuates tumor necrosis factor-α-induced protein-tyrosine phosphatase-1B production in HepG2 cells

  • J. Wu
  • L.-J. Yang
  • D.-J. ZouEmail author
Original Article
  • 68 Downloads

Abstract

Tumor necrosis factor (TNF)-α impairs insulin signaling and plays an important role in the development of insulin resistance. The underlying molecular mechanism by which TNF-α regulates hepatic protein-tyrosine phosphatase (PTP)-1B expression is not well understood. Rosiglitazone is used as a drug to improve insulin sensitivity in vivo. However, its effect on TNF-α-induced PTP-1B expression remains to be explored. In the present study, we sought to identify the mechanism of TNF-α-regulated hepatic PTP-1B expression and evaluate the effect of rosiglitazone on TNF-α-induced hepatic PTP-1B upregulation. TNF-α up-regulates PTP-1B expression in a dose-dependent manner and decreases insulin-stimulated phosphorylation of IR and insulin receptor substrate-1 in HepG2 cells. TNF-α increases p65 protein level and nuclear factor κB (NF-κB) activity. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate impairs TNF-α-induced PTP-1B upregulation. Rosiglitazone significantly blocks TNF-α-induced PTP-1B upregulation and NF-κB activation. Our data strongly suggest that TNF-α-induced PTP-1B over-expression may contribute to hepatic IR in obesity and diabetes, and NF-κB is involved in rosiglitazone attenuated PTP-1B upregulation by TNF-α.

Key-words

NF-κB PTP-1B rosiglitazone TNF-α 

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Copyright information

© Italian Society of Endocrinology (SIE) 2012

Authors and Affiliations

  1. 1.Department of Endocrinology, Changhai HospitalThe Second Military Medical UniversityShanghaiChina
  2. 2.Department of Oncology, Chang Hai Hospitalthe Second Military Medical UniversityShanghaiPR China

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