Open Access

IKKβ suppression of TSC1 function links the mTOR pathway with insulin resistance

  • Authors: Dung-Fang Lee, Hsu-Ping Kuo, Chun-Te Chen, Yongkun Wei, Chao-Kai Chou, Jen-Yu Hung, Chia-Jui Yen, Mien-Chie Hung
  • View Affiliations

  • Published online on: Saturday, November 1, 2008
  • Pages: 633-638
  • DOI: 10.3892/ijmm_00000065

Abstract

The proinflammatory cytokine TNFα is one of the factors that links obesity-derived chronic inflammation with insulin resistance. Activation of mTOR signaling pathway has been found to suppress insulin sensitivity through serine phosphorylation and the inhibition of IRS1 by mTOR and its downstream effector, S6K1. It remains elusive that whether the mTOR pathway has a role in TNFα-mediated insulin resistance. In the present study, we demonstrated that TNFα-IKKβ-mediated inactivation of TSC1 resulted in increasing phosphorylation of IRS1 serine 307 and serine 636/639, impaired insulin-induced glucose uptake, tyrosine phosphorylation of IRS1, and the association between IRS1 and PI3K p85. Furthermore, a higher expression of pIKKβ (S181), pTSC1(S511), and pS6(S240/244) was found in livers obtained from both C57BL/6J mice on a high-fat diet and B6.V-Lepob/J mice. Collectively, dysregulation of the TSC1/ TSC2/mTOR signaling pathway by IKKβ is a common molecular switch for both cancer pathogenesis and diet- and obesity-induced insulin resistance.
Journal Cover

November 2008
Volume 22 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
(total number of cites)

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APA
Lee, D., Kuo, H., Chen, C., Wei, Y., Chou, C., Hung, J., Yen, C., & Hung, M. (2008). IKKβ suppression of TSC1 function links the mTOR pathway with insulin resistance. International Journal of Molecular Medicine, 22(5), 633-638.
MLA
Lee, Kuo, Chen, Wei, Chou, Hung, Yen, and Mien-Chie Hung. "IKKβ suppression of TSC1 function links the mTOR pathway with insulin resistance." International Journal of Molecular Medicine International Journal of Molecular Medicine 22.5 (2008): 633-638.
Chicago
Lee, Kuo, Chen, Wei, Chou, Hung, Yen, and Mien-Chie Hung. "IKKβ suppression of TSC1 function links the mTOR pathway with insulin resistance." International Journal of Molecular Medicine International Journal of Molecular Medicine 22 no. 5 (2008): 633-638.