Figure 5.

NMN administration ameliorates the defects in Nampt^+/− mice and islets. A) IPGTTs after NMN administration. The same Nampt^+/− (n=18) and control (n=19) cohorts that were used for the IPGTTs shown in Figure 4C were injected with NMN (500 mg/kg body weight) ∼14 hrs prior to IPGTTs. B) Plasma insulin levels in Nampt^+/− and control female littermates at 0, 15, and 30 min time points in IPGTTs. Nampt^+/− mice (n=16), control mice (n=17) for 0 and 30 min time points; Nampt^+/− mice (n=10), control mice (n=8) for 15 min time point. C) Insulin secreted (ng/ml/hr) from NMN-treated Nampt^+/− and control islets at the indicated glucose concentrations (n=4 mice for each genotype). Isolated primary islets were cultured overnight in the RPMI media containing 1 μM nicotinamide plus 50 μM NMN prior to insulin secretion experiments. D) NAD levels (pmole) in wild-type primary islets treated overnight with NMN, FK866, or the combination of these compounds at the indicated concentrations. NAD levels were measured by HPLC in triplicates of primary islets pooled from four individual wild-type mice. E) Insulin secreted (ng/ml/hr) at the indicated glucose concentrations from control, FK866-treated, and FK866 plus NMN-treated wild-type primary islets. The experiments were conducted in triplicates of primary islets pooled from four individual mice cultured for 48h in the RPMI media containing 1 μM nicotinamide and indicated compounds (10 nM for FK866 and 100 μM for NMN) prior to insulin secretion experiments.

All results are expressed as mean ± SEM. *p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.