ShK-186 reduces hyperglycemia and improves glucose tolerance in mice fed the obesity-inducing diet. (A and B) Blood sugar (A, Student t test; P = 0.002) and HbA1c (B, Student t test; P = 0.012). (C) Intraperitoneal glucose tolerance test: AUCcontrols = 42,075 mg/dL × min; AUCtreated = 31,420 mg/dL × min; repeated-measures two-way ANOVA with post hoc Bonferroni correction: 60 min: ***P < 0.001. (D) Fasting insulin levels in controls (3.2 ± 0.9 ng/mL) and ShK-186–treated mice (1.2 ± 0.1 ng/mL); Student t test; **P < 0.03. (E) Fold-increase in insulin release shown as the ratio of the insulin level 15 min after glucose challenge vs. the level before glucose challenge. (F) Insulin tolerance test to measure peripheral insulin sensitivity: AUCcontrol = 26,525 mg/dL × min; AUCtreated = 20,818 mg/dL × min, repeated-measures two-way ANOVA with post hoc Bonferroni correction, 120 min: ***P < 0.001. Measurements at week 10 of the study; n = 6–8 mice in each group. All graphs depict mean ± SEM.