Reversal of obesity- and diet-induced insulin resistance with salicylates or _targeted disruption of Ikkbeta
- PMID: 11533494
- DOI: 10.1126/science.1061620
Reversal of obesity- and diet-induced insulin resistance with salicylates or _targeted disruption of Ikkbeta
Erratum in
- Science 2002 Jan 11;295(5553):277
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 IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular _target. Heterozygous deletion (Ikkbeta+/-) 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 IKKbeta pathway as a _target for insulin sensitization.
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