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Overactivation of NF-κB impairs insulin sensitivity and mediates palmitate-induced insulin resistance in C2C12 skeletal muscle cells

Endocrine volume 37, pages 157–166 (2010)Cite this article

Abstract

Lipid-induced insulin resistance is associated with inflammatory state in epidemiological studies. However, it is still unclear whether the activation of NF-κB, a pivotal transcription factor of inflammation, plays a crucial role in mediating skeletal muscle insulin resistance. This study addressed what was the role of NF-κB in lipid-induced insulin resistance and whether NF-κB activation was sufficient to cause insulin resistance in C2C12 myotubes. A 16 h exposure of myotubes to palmitate reduced net insulin-stimulated glucose uptake by 48%, GLUT4 translocation by 52%, Akt phosphorylation by 54%, induced a 1.8-fold increase in insulin-stimulated insulin receptor substrate (IRS) phosphorylation, and doubled NF-κB activation. Myotubes transfected with NF-κB p65 siRNA for 24 h and followed by a treatment with palmitate for 16 h efficiently blocked NF-κB activation, and prevented the detrimental effects of palmitate on the metabolic actions of insulin. Transfection of myotubes with I-κBα siRNA for 24 h also led to a twofold induction of NF-κB activation, and reduced net insulin-stimulated glucose uptake by 30%, GLUT4 translocation by 35%, Akt phosphorylation by 31%, induced a 0.7-fold increase in insulin-stimulated IRS phosphorylation. These findings suggest that NF-κB overexpression per se is sufficient to impair insulin sensitivity and palmitate-induced insulin resistance is mediated by NF-κB in skeletal muscle cells.

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Acknowledgment

The study was supported by the Natural science foundation of Guangdong Province, China (Grant No. 7001282).

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Affiliations

  1. Department of Endocrinology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China

    Jingwen Zhang, Ying Guo & Helin Ding

  2. Department of Endocrinology, Guangdong General Hospital, Guangzhou, 510080, China

    Wen Wu

  3. Research Centre, Guangdong General Hospital, Guangzhou, 510080, China

    Dongfeng Li

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  1. Jingwen Zhang
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  2. Wen Wu
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  3. Dongfeng Li
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  4. Ying Guo
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Correspondence to Helin Ding.

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Zhang, J., Wu, W., Li, D. et al. Overactivation of NF-κB impairs insulin sensitivity and mediates palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Endocr 37, 157–166 (2010). https://doi.org/10.1007/s12020-009-9283-y

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  • DOI: https://doi.org/10.1007/s12020-009-9283-y

Keywords

  • Small Interfering RNA
  • Skeletal muscle
  • Insulin resistance
  • Palmitate
  • NF-kappa B
  • I-kappa B