Male InsrT1150A and WT littermate mice were fed an HFD for 8 to 10 days and fasted overnight before hyperinsulinemic-euglycemic clamp studies. (A) Glucose infusion rate. (B) Mean steady-state glucose infusion rate. (C) EGP during the basal and the steady-state periods of the clamp. (D) Insulin suppression of EGP during the clamp. (E and F) Phosphorylation of INSR, AKT, and GSK3β in overnight-fasted (– insulin, basal) or post-clamp (+ insulin, clamp) mice. (G) Immunoprecipitable liver IRK activity in post-clamp mice. *P < 0.05 and **P < 0.005, by unpaired, 2-tailed Student’s t test. Data represent the mean ± SEM. n = 6 mice per group.