Inflammation and the IKKβ/IκB/NF-κB axis in obesity- and diet-induced insulin resistance (original) (raw)

International Journal of Obesity volume 27, pages S49–S52 (2003)Cite this article

Abstract

Antidiabetic effects associated with salicylates have been known for years, although the underlying mechanisms were not understood. We have been reinvestigating these effects in the light of recent discoveries in the areas of signal transduction and insulin resistance. Our findings showed that signaling pathways leading to I_κ_B kinase β (IKK_β_) and NF-κ_B are activated in insulin-responsive tissues of obese and high-fat-fed animals. Since activation correlates with the development of insulin resistance, we asked whether signaling through this might be involved in the pathogenesis of insulin resistance. Heterozygous gene deletion (Ikkβ+/−) or salicylates, working as IKK_β inhibitors, improved insulin sensitivity in insulin-resistant rodent models. Furthermore, high doses of salicylates (aspirin or salicylate) improved insulin sensitivity in patients with type II diabetes. Our studies implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type II diabetes mellitus and identify the IKK_β_/NF-_κ_B pathway as a molecular mediator of insulin resistance and pharmacological target for insulin sensitization.

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Authors and Affiliations

  1. Joslin Diabetes Center & Department of Medicine, Harvard Medical School, Boston, MA, USA
    S E Shoelson, J Lee & M Yuan

Authors

  1. S E Shoelson
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  2. J Lee
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  3. M Yuan
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Correspondence toS E Shoelson.

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Shoelson, S., Lee, J. & Yuan, M. Inflammation and the IKK_β_/I_κ_B/NF-_κ_B axis in obesity- and diet-induced insulin resistance.Int J Obes 27 (Suppl 3), S49–S52 (2003). https://doi.org/10.1038/sj.ijo.0802501

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