SST5 agonist, CRN02481, increases plasma glucose and decreases insulin secretion in both WT and Sur1−/−KATP-HI mouse models after glucose challenge.A, glucose tolerance test (GTT) in WT mice treated with vehicle or CRN02481 (30 mg/kg) by gavage followed by I.P. injection of 2 g/kg glucose. Two-way ANOVA with Tukey’s multiple comparisons: (F(1, 60) = 80.45, p < 0.0001). (n = 7) (B) Area under the curve (AUC) calculation for GTT of WT mice. One way ANOVA: (F(1, 12) = 15.98, p = 0.002). C, plasma insulin levels of WT mice during 0, 30, and 60 min time points during GTT. One-way ANOVA: 0 min (F(1, 12) = 0.005, p = 0.94); 30 min (F(1, 12) = 30.88, p = 0.0001); 60 min (F(1, 12) = 12.43, p = 0.004). D, GTT in Sur1−/− mice treated with vehicle or CRN02481 (30 mg/kg) by gavage followed by I.P. injection of 2 g/kg glucose. Two-way ANOVA with Tukey’s multiple comparisons: (F(1, 60) = 124.3, p <0.0001) (n = 7). E, AUC calculated for Sur1−/− mice GTT. One-way ANOVA: (F(1, 12) = 56.67, p = 6.97 × 10-6). F, plasma insulin levels of Sur1−/− mice during 0, 30, and 60 min time points during GTT. One-way ANOVA: 0 min (F(1, 12) = 0.105, p = 0.75); 30 min (F(1, 12) = 13.16, p = 0.003); 60 min (F(1, 12) = 6.67, p = 0.02). (n = 7) (Comparison to vehicle control: ∗∗∗p < 0.001; ∗∗p <0.01; p < 0.05). Data represent mean ± SD. WT, wild type.