treated with tnf u03b1 similar effects were seen with akt tnf u03b1 treatment reduced akt activation 18 u00b1 15 and this was reversed by ikk u03b2 k44a expression 174 u00b1 38 active ikk kinases thus mediate u2018 insulin resistance u2019 in cultured cells and the inactive kinases act as dominant inhibitors to block tnf u03b1 induced insulin resistance the consistent ability of dominant inhibitory ikk u03b2 to elevate ir signaling well above the normal level indicates that ikk inhibits insulin signaling even in the absence of tnf u03b1 there is in vivo support for this as well fa rats and ob mice see fig1 and sprague dawley rats that are not insulin resistant obese or diabetic show increased insulin sensitivity in response to aspirin treatment studies were conducted with mice having targeted disruption of the ikk u03b2 locus ikk u03b2 u2212 u2212 mice die in utero days e12 5 to e14 due to enhanced liver apoptosis li et al 1999 science 284 321 325 however heterozygous ikk u03b2 u2212 mice seem to be normal ikk u03b2 u2212 and lep ob ob mice were crossed to reduce ikk u03b2 gene dose in insulin resistant animals while there were no significant effects on fasting blood glucose levels in ikk u03b2 u2212 lep and ikk u03b2 u2212 lepob mice compared to ikk u03b2 lep and ikk u03b2 lepob littermate controls fasting blood glucose levels were significantly reduced in ikk u03b2 u2212 lepob ob mice 248 u00b1 17 mg dl compared to ikk u03b2 lepob ob littermates 346 u00b1 23 mg dl p 0 0023 fig2 panel a glucose tolerance in the ikk u03b2 u2212 lepob ob mice was improved at every time point fig2 panel b insulin levels.