Fig. 4: The systemic effect of AZD1656 treatment in db/db animals.

a, Representative images of control, db/db and AZD-treated db/db mice from the study. b, Body weight (control n = 23, db/db n = 17, AZD n = 20) multiple group comparison by one-way ANOVA (control versus db/db P = 0.0001, control versus AZD P = 0.0001, db/db versus AZD P = 0.623). c, Fasting plasma glucose (n = 9 per group). Control versus db/db P = 0.0001, control versus AZD P = 0.0001, db/db versus AZD P = 0.47. d, Plasma insulin (control n = 10, db/db n = 11, AZD n = 6; control versus db/db P = 0.0001, control versus AZD P = 0.0010; db/db versus AZD P = 0.8874). e–g, Circulating lipid metabolism constituents (free fatty acids (control n = 11, db/db n = 9, AZD n = 5) (e), cholesterol (control n = 7, db/db n = 10, AZD n = 5) (f), triacylglycerol (control n = 7, db/db n = 11, AZD n = 9) (g)). Multiple group comparison by one-way ANOVA (*P < 0.05, **P < 0.01, ***P < 0.001). Liver phenotype profiling. h, Liver weight (control n = 12, db/db n = 11, AZD n = 7). Multiple group comparison by one way ANOVA. i, Fold change db/db versus control liver 1H NMR metabolomic spectroscopy profiling. Two group comparison by two-tailed t-test. j, Fold change AZD versus control liver 1H NMR metabolomic spectroscopy profiling (control n = 6, db/db n = 7, AZD n = 7). Skeletal muscle phenotype (control n = 6, db/db n = 6, AZD n = 5), two group comparison by two-tailed t-test P < 0.05. k, Lean muscle mass by body composition analysis (n = 5 per group; control versus db/db P = 0.0001, control versus AZD P = 0.0001, db/db versus AZD P = 0.02). Multiple group comparison by one-way ANOVA. l, Fold change db/db versus control skeletal muscle 1H NMR metabolomic spectroscopy profiling. m, Fold change AZD versus control skeletal muscle 1H NMR metabolomic spectroscopy profiling (n = 5 per group). Two group comparison by two-tailed t-test. *P < 0.05, **P < 0.01, ***P < 0.001 multiple group comparison by one-way ANOVA, two-tail comparison by Student’s t-test. Of note, parameters measured over the course of the six-year study in multiple cohorts thus sample size varied. n represents biological replicates (individual animals). Data are presented as mean ± s.e.m. Metabolite fold change versus control (control = 1) with propagated error of mean.