The hepatic expressions of insulin receptor substrates, like IRS1, IRS2, and AKT2, fundamental in glucose homeostasis,21 were significantly decreased in F2–F4 with respect to those with less severe forms of MASLD, in both diabetic and non-diabetic groups (Figures 4A–4C), consistently with the increased Hep-IR observed in Figures 1E and 2F. Moreover, their expression was inversely correlated with the intracellular glucose fluxes (Figure 4D). Here, AKT2 is linked to metabolic dysfunction-associated steatotic liver disease.