Fig. 2.

MLN4924 treatment acutely decreases hepatic glucose production in mice. (A and B) Male C57BL/6J mice were treated with 60 mg/kg MLN4924 via SQ injection at 5 PM on day 1 and 9 AM on day 2. Mice were fasted from 9 AM to 3 PM on day 2 and euthanized. Effect of MLN4924 on hepatic cullin neddylation was measured by Western blotting shown in A. Densitometry is shown in B. The red arrows indicate neddylated cullin bands. (C–F) Male C57BL/6J mice on chow diet (C and D) or WD for 4 wk (E and F) were administered 60 mg/kg MLN4924 as described in A. PTT or GTT were performed as described in Materials and Methods. Results are expressed as mean ± SEM (n = 4 to 5). *P < 0.05 versus Vehicle group at the same time point. Unpaired Student’s t test was used to calculate the P value.