Sci. Aging Knowl. Environ., 3 October 2001
Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikk
Minsheng Yuan, Nicky Konstantopoulos, Jongsoon Lee, Lone Hansen, Zhi-Wei Li, Michael Karin, and Steven E. Shoelsonhttp://sageke.sciencemag.org/cgi/content/abstract/sageke;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 IB kinase (IKK) attenuated insulin signaling in cultured cells, whereas IKK inhibition reversed insulin resistance. Thus, IKK, 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 pathway as a target for insulin sensitization.
Science of Aging Knowledge Environment. ISSN 1539-6150