Insulin only moderately (~1.5–2 –fold) induced S6 (P-S6) and Akt (P-Akt) phosphorylation in HFD-fed WT mice (compare lane 1–2 with lane 3–4, for quantification see Fig 4E and 4F), which is indicative of HFD-induced insulin resistance [56, 58–60]. The gene discussed is INS; the disease is Insulin resistance.