That diet‐induced increases in hepatic aPKC activity over 2–3 months (Figure 3) selectively impairs insulin‐stimulated recruitment of Akt to the WD40/ProF platform and phosphorylation/inhibition of FoxO1 and PGC‐1α, provides a unique mechanism for linking dietary excesses of fats in HFF mice, and carbohydrates in ob/ob mice and obese/T2DM monkeys, to increases in hepatic gluconeogenesis, and development of systemic insulin resistance and hyperinsulinemia. The gene discussed is AKT1; the disease is Insulin resistance.