In addition, we recently found that failure of the existing hyperinsulinemia in these HFF mice to increase conventional PKC‐α/β activity in liver, coupled with strong stimulatory effects of supplemental insulin thereupon, suggests a partial, but surpassable (via spare receptors), impairment in hepatic IRs; accordingly, as discussed below, it appears that IR abnormalities may result from HFD‐induced increases in hepatic aPKC activity at early stages of development of insulin resistance. The gene discussed is INS; the disease is hyperinsulinism.