(A–C) Hyperinsulinemic-euglycemic clamp studies in Rap1ΔSF1 and littermate control mice fed an HFD for 18 weeks (n = 4–5). Shown are the GIR (A), peripheral glucose disposal rate (B), and 2-deoxy-d-glucose (2DG) uptake (C). (D) Western blot (left) and quantification (right) of AKT (Thr308) and glycogen synthase kinase-3β (Ser9) phosphorylation in liver, fat, and muscle at 10 minutes after a bolus injection of insulin (1 U/kg, i.p.) or saline into Rap1ΔSF1 or control mice fed an HFD for 35 weeks. See complete unedited blots in the supplemental material. *P < 0.05 for 2-tailed t tests (A–C) or 2-way ANOVA followed by Bonferroni’s multiple comparisons tests (D). All error bars are mean ± SEM.