IRS1 and hyperinsulinism: However, earlier, at 3–4 weeks of consuming a “Western” 40%‐fat‐kcal diet (Figure 3), increases in hepatic gluconeogenic enzymes, PEPCK/G6Pase, are not apparent,17 and hyperinsulinemia here apparently largely reflects other pathogenetic mechanisms, including impaired insulin action on IRS‐1/PI3K, Akt, aPKC, and glucose transport in muscle,17 and perhaps IR impairment (see below).