Resistance of cells to the actions of insulin is a prominent feature of type 2 diabetes. As early as 1876, reports emerged that high doses of aspirin could help decrease concentrations of glucose in the blood of diabetic patients, an action that could reflect enhanced insulin action in target cells. Yuan et al. are finally able to provide a mechanism that may explain this effect. Their studies show that aspirin in high doses inhibits the protein kinase IKKβ, which mediates the actions of pro-inflamatory cytokines. Furthermore, heterozygous mice that had lost one allele encoding IKKβ were protected against insulin resistance when fed a high-fat diet. Thus, IKKβ may be a useful target for therapeutic agents designed to ameliorate insulin resistance.
M. Yuan, N. Konstantopoulos, J. Lee, L. Hansen, Z.-W. Li, M. Karin, S. E. Shoelson, Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293, 1673-1677. [Abstract] [Full Text]