Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikkβ

ArticleinScience 293(5535):1673-7 · September 2001with108 Reads
Impact Factor: 33.61 · DOI: 10.1126/science.1061620 · Source: PubMed


    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 Lepob/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.