Fig. 7: Alterations in Vav2 catalytic activity alter short-term responses to glucose.

a Response of 6-month-old mice of the indicated genotypes and diet conditions (inset) to the infusion of a bolus of glucose. The HFD was maintained for 4 months. CD chow diet. Data represent the mean ± SEM. *, P = 0.0291; **, P = 0.0023 (HFD- vs. CD-fed Vav2^L332A/L332A mice, 0 min) and P = 0.0021 (CD-fed Vav2^L332A/L332A mice, 90 min); ***, P = 0.0003 (HFD-fed WT mice, 0 min), P = 0.00009 (HFD-fed WT mice, 120 min), P = 0.0004 (HFD-fed WT mice, 150 min), P = 0.00001 (CD-fed Vav2^L332A/L332A mice, 30 min), P = 0.0005 (HFD-fed Vav2^L332A/L332A mice, 30 min), and P < 0.000001 (rest of analyses) relative to chow-fed WT animals (in the case of CD-fed Vav2^L332A/L332A and HFD-fed WT mice) or HFD-fed WT animals (in the case of experiments with HFD-fed Vav2^L332A/L332A animals) using two-way ANOVA and Holm–Sidak multiple comparison tests. n = 14 (CD-fed WT) and 15 (others) mice per group from three independent experiments. b Areas under the curve (AUC) obtained in the glucose tolerance tests carried out in mice of the indicated genotypes (inset), diet conditions (inset), and ages (bottom). Data represent the mean ± SEM. **, P = 0.0041; ***, P = 0.00009 (CD-fed Vav2^L332A/L332A vs. HFD-fed WT mice, 4 months), 0.0002 (CD-fed Vav2^L332A/L332A vs. CD-fed WT mice, 2 months), 0.000004 (CD-fed Vav2^L332A/L332A vs. HFD-fed WT mice, 2 months) and P < 0.000001 (rest) relative to the control at each time-point using two-way ANOVA and Holm–Sidak multiple comparison tests (n = 15 mice per group and genotype utilized in three independent experiments). c Response of CD-fed 4-month-old mice of the indicated genotypes to insulin. Data represent the mean ± SEM. ***, P = 0.00007 (15 min) and 0.0009 (30 min) relative to the value control at each time-point using two-tailed Student’s t tests. n = 16 (WT) and 15 (Vav2^L332A/L332A) animals used in three independent experiments). d AUC responses of CD-fed mice of indicated genotypes (inset) and ages (bottom) to the infusion of insulin. Data are presented as mean ± SEM. *, P = 0.0271; **, P = 0.006; ***, P = 0.0009 (4-month-old mice) and P < 0.000001 (6-month-old mice) relative to the values obtained in the appropriate control samples using two-tailed Student’s t tests. n = 5 (3-month-old WT and 5-month-old), 6 (3-month-old Vav2^L332A/L332A), 16 (4-month-old) and 21 (6-month-old) mice. e Response of HFD-fed 6-month-old mice of the indicated genotypes maintained for 4 months in HFD to the infusion of insulin. Data are shown as mean ± SEM. *, P = 0.0255; **, P = 0.0058 (15 min), P = 0.0022 (30 min), P=0.0091 (90 min), and P = 0.0020 (120 min) relative to the value obtained in control samples in same time-point using two-tailed Student’s t tests (n = 5 mice per experimental condition). f Glucose infusion rates found in 3-month-old animals of the indicated genotypes. Data are shown as mean ± SEM. *, P = 0.0312 (10, 110, 120, 130, 140, 150, 160, and 170 min), P = 0.0231 (20 and 30 min), P = 0.0157 (90 min), and P = 0.0236 (100 min); **, P = 0.0028 (40 min), P = 0.0013 (60 min), P = 0.0047 (70 min), and P = 0.0082 (80 min); ***, P = 0.0006 relative to value obtained in control samples in same time-point using two-tailed Student’s t tests. n = 6 (WT) and 8 (Vav2^L332A/L332A) mice. g Basal levels of glucose in CD-fed animals of the indicated genotypes (inset) and ages (bottom) that were fasted overnight. Data are shown as mean ± SEM. *, P = 0.0465 (8-month-old mice) and 0.0352 (12-month-old mice) relative to control samples using two-tailed Student’s t tests. n = 5 (12-month-old), 6 (8-month-old WT), 7 (6- and 8-month-old Vav2^L332A/L332A), 12 (6-month-old WT), 15 (4-month-old Vav2^L332A/L332A), and 16 (4-month-old WT) mice. h Representative response of 6-month-old mice of indicated genotypes and diet conditions (inset) to the infusion of glucose. Data are shown as mean ± SEM. *, P = 0.0142 (HFD-fed WT mice, 30 min), P = 0.0244 (CD-fed Vav2^Onc/Onc mice, 30 min), P = 0.05 (CD-fed Vav2^Onc/Onc mice, 60 min), P = 0.0211 (CD-fed Vav2^Onc/Onc mice, 120 min), P = 0.0497 (CD-fed Vav2^Onc/Onc mice, 150 min), P = 0.0136 (CD-fed Vav2^Onc/Onc mice, 180 min), P = 0.0244 (HFD-fed Vav2^Onc/Onc mice, 60 min), and P = 0.0254 (HFD-fed Vav2^Onc/Onc mice, 90 min); **, P = 0.0057 (HFD-fed WT mice, 60 min), P = 0.0026 (HFD-fed WT mice, 120 min), P = 0.0029 (HFD-fed WT mice, 150 min), P = 0.0037 (HFD-fed WT mice, 180 min), P = 0.0013 (CD-fed Vav2^Onc/Onc mice, 0 min), P = 0.0087 (HFD-fed Vav2^Onc/Onc mice, 120 min), P = 0.0068 (HFD-fed Vav2^Onc/Onc mice, 150 min), and P = 0.0029 (HFD-fed Vav2^Onc/Onc mice, 180 min); ***, P = 0.0007 relative to either CD-fed WT animals (in the case of CD-fed Vav2^Onc/Onc and HFD-fed WT mice) or HFD-fed WT animals (in the case of HFD-fed Vav2^Onc/Onc mice) using two-way ANOVA and Holm–Sidak multiple comparison tests (n = 5 animals per experimental group). i AUC responses of mice of indicated genotypes (inset), ages (bottom), and diet conditions (inset) to the infusion of glucose. Data represent the mean ± SEM. *, P = 0.0337; **, P = 0.007; ***, P = 0.0001 (HFD-fed Vav2^Onc/Onc mice, 2 months) and P < 0.000001 (rest of analyses) relative to the control at each time-point using two-way ANOVA and Holm–Sidak multiple comparison test. n = 15 (HFD-fed Vav2^Onc/Onc, CD-fed WT controls for 2 and 4 months and CD-fed Vav2^Onc/Onc, 4 months), 16 (HFD-fed, 2 months), 17 (HFD-fed WT, 3 and 4 months), and 18 (CD-fed, 3 months) animals per group. j Representative response of CD-fed 4-month-old mice of indicated genotypes (inset) to the infusion of insulin. Data represent the mean ± SEM. **, P = 0.0092 relative to values obtained in control samples in the same time-point and normalized to basal using two-tailed Student’s t tests. n = 7 (WT) and 6 (Vav2^Onc/Onc) mice. k Response of 6-month-old mice of indicated genotypes (inset) and maintained under HFD for 4 months to the infusion of insulin. Data are shown as mean ± SEM. n = 8 (WT) and 5 (Vav2^Onc/Onc) mice. Source data for this figure are provided as a Source data file.