A and B, GTT was carried out in wild-type (WT) and Nedd4+/− (Het) mice on ND. Mice fasted overnight were ip injected with glucose at 1.5 g/kg body weight. Blood glucose levels were measured at time 0 and then 30, 60, 90, and 120 minutes after glucose injection. Glucose clearance ability was similar between genotypes for males (A) or females (B) (n = 7–11). C and D, After a 4-hour fast, mice received ip insulin 0.75 U/kg body weight, and then blood glucose was measured at 0, 30, 60, and 90 minutes relative to insulin injection. Het mice were less responsive to insulin (vs WT littermate controls), based on glucose clearance rate in males (A) and females (B) (n = 8–11). E, Serum insulin levels at time 0, 30, and 60 minutes after glucose injection during GTT (n = 8; 4 males and 4 females). Data represent mean ± SEM. *, P < .05; **, P < .01; and ***, P < .001.