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 IκB kinase β (IKKβ) and NF-κB 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 IKKβ 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 IKKβ/NF-κB pathway as a molecular mediator of insulin resistance and pharmacological target for insulin sensitization.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shoelson, S., Lee, J. & Yuan, M. Inflammation and the IKKβ/IκB/NF-κB 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
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0802501
Keywords
This article is cited by
-
Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus
Probiotics and Antimicrobial Proteins (2023)
-
Insights on the role of anti-inflammatory and immunosuppressive agents in the amelioration of diabetes
Diabetology International (2023)
-
A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease
Neurochemical Research (2023)
-
Anti-obesity effects of Lactiplantibacillus plantarum SKO-001 in high-fat diet-induced obese mice
European Journal of Nutrition (2023)
-
Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications
Nature Reviews Cardiology (2022)