Restoration of macrophage A2bAR improves glucose clearance, insulin sensitivity and reduces glucose levels following HFD.

<p>Glucose and insulin levels were measured in WT, A2bAR KO, and CD68-Tg mice at 28 weeks of age, following 16 weeks of HFD. Data are averages ± SD. *Student two-tail t-test assuming equal variance was found significant only when p-value <0.05. A. Glucose clearance in the blood post glucose overload (n = 12/group), Data in a. were analyzed by ANOVA followed by Bonferroni comparison test with the following p-values for indicated time points, Time 0 min: p-value <0.0001; WT vs CD68-Tg p-value <0.05, WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.01. Time 60 min: p-value 0.003487; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.01, CD68-Tg vs A2bAR KO p-value <0.01. Time 90 min: p-value 0.005068; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.01, CD68-Tg vs A2bAR KO p-value <0.05. Time 90 min: p-value 0.005855; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.05. B. Insulin levels in the plasma post glucose overload during the glucose tolerance test (n = 12/group). Data in b. were analyzed by ANOVA followed by Bonferroni comparison test with the following p-values for indicated time points. Time 0 min: p-value 0.017963; WT vs CD68-Tg p-value <0.05, WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO n.s. Time 20 min: p-value 0.017304; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.05. Time 120 min: p-value 0.019056; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO n.s. C. Glucose clearance in the plasma post insulin overload (n = 12/group). Data in c. were analyzed by ANOVA followed by Bonferroni comparison test with the following p-values for indicated time points. Time 0 min: p-value 0.006653; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.01. Time 15 min: p-value 0.017975; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.05. Time 30 min: p-value 0.016828; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.05. Time 120 min: p-value 0.003444; WT vs CD68-Tg n.s., WT vs A2bAR KO p-value <0.05, CD68-Tg vs A2bAR KO p-value <0.01. D. Plasma glucose levels 16 hours post starvation (n = 12/group). WT vs A2bAR KO, p-value = 0.0404; WT vs CD68-Tg, p-value = 0.0074; CD68-Tg vs A2bAR KO, p-value = 0.0026. E. Plasma insulin levels 16 hours post starvation (n = 12/group), WT vs A2bAR KO p-value = 0.0175.