TLR9 deficiency protects NOD mice from diabetes development and enhances beta cell function. (a, b) The natural history of diabetes development in female (a) and male (b) Tlr9−/− NOD mice (black circles; female, n = 25, and male, n = 26, mice) and Tlr9+/+ NOD littermates (white circles; female, n = 16, and male, n = 9, mice). (a) p = 0.004 and (b) p = 0.0025. (c, d) IPGTTs were performed in 5–6-week-old female Tlr9−/− NOD mice (black circles, n = 4 mice) and Tlr9+/+ NOD littermates (white circles, n = 5 mice). Blood glucose measurements at different time points after glucose injection (c) (p = 0.0002) and AUC for glucose (d) (p = 0.024) are shown. (e, f) IPGTTs were performed in 5–6-week-old female Tlr9−/− NOD mice (n = 4 mice) and Tlr9+/+ NOD.Scid (NSc) mice (n = 5 mice). Blood glucose measurements (e) and AUC (f) are shown. The experiments shown in (a) were performed twice with very similar results and one of the two experiments is shown. The experiments shown in (c–f) were performed three times and the results from one of the three experiments are shown. Data in (c–f) are expressed as means (SD). Data were analysed in (a, b) by logrank test for survival, (c, e) by two-way ANOVA and in (d, f) by two-tailed unpaired Student’s t test. *p < 0.05, **p < 0.01, ***p < 0.001