Sci. Aging Knowl. Environ., 3 October 2001
Vol. 2001, Issue 1, p. or7


Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikk{beta}

Minsheng Yuan, Nicky Konstantopoulos, Jongsoon Lee, Lone Hansen, Zhi-Wei Li, Michael Karin, and Steven E. Shoelson;2001/1/or7

Abstract: Science 293, 1673-1677 (2001).

We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the I{kappa}B kinase (IKK{beta}) attenuated insulin signaling in cultured cells, whereas IKK{beta} inhibition reversed insulin resistance. Thus, IKK{beta}, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikk+/-) 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 IKK{beta} pathway as a target for insulin sensitization.

Full Text

Science of Aging Knowledge Environment. ISSN 1539-6150