Interestingly, in concert with our findings, knockout of hepatic WD40/ProF (aka, WDFY2) diminishes insulin‐stimulated FoxO1 phosphorylation, increases gluconeogenic enzyme expression, and produces systemic insulin resistance; however, consequences of this knockout are more drastic than the functional changes in WD40/ProF induced by hyperactivity of hepatic aPKC in that total cellular activity of IRS‐1/PI3K‐dependent Akt2 is diminished in these knockout mice.58 This evidence concerns the gene IRS1 and Insulin resistance.