Despite these hallmarks of improved glucose metabolism as well as the amelioration of hepatic steatosis in ob/ob HKO mice, these animals manifested exacerbated hyperglycemia and hyperinsulinemia (Figure 2, B and C) without an apparent change in hepatic insulin signaling, as assessed on the basis of Akt phosphorylation at Ser473 (Supplemental Figure 4G) in the fed state compared with ob/ob F/F mice. Here, INS is linked to hyperinsulinism.