Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikkβ
Top Cited Papers
- 31 August 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 293 (5535) , 1673-1677
- https://doi.org/10.1126/science.1061620
Abstract
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IκB kinase β (IKKβ) attenuated insulin signaling in cultured cells, whereas IKKβ inhibition reversed insulin resistance. Thus, IKKβ, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion ( Ikkβ +/− ) protected against the development of insulin resistance during high-fat feeding and in obese Lep ob/ob mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKβ pathway as a target for insulin sensitization.Keywords
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