AG490 Prevents and Reverses Diabetes Figure 1. AG490 prevents development of autoimmune diabetes. Prediabetic female NOD mice at 4 (UT: n = 11; DMSO: n = 13; and AG490 treated mice: n = 15 mice/group) (A), or at 8 week of age, (n = 10 per group) (B) were treated with AG490 or DMSO (i.p) for 5 consecutive week, three time per week followed by once a week for 5 more week [Kaplan-Meier test (*p = 0.02, 1A) and (**p = 0.005, 1B, at week 30)]. Our data also indicate that significant differences (p,0.01) was observed between the AG490 and DMSO treated mice for up week 52; when treatment was started at week 4. Body weight of NOD mice treated with AG490 (C) or DMSO (D) in mice when treatment initiated from 4 weeks of age is shown. [This figure is intended to be in color online and black and white in print.] doi:10.1371/journal.pone.0036079.g001 The C-peptide concentration of AG490 treated NOD (8 week group) was significatly higher than the C-peptide level of mice when treatment was initiated at 4 weeks of age. In a separate experiment, female NOD mice were treated either with AG490 or DMSO for 5 weeks and then were sacrificied at week 10. Total RNA extracted from enriched infiltrating leukocytes from Figure 2. AG490 induces remission of diabetes in NOD and in STZ-induced diabetic mice. Newly diagnosed and established diabetic NOD mice were treated with AG490 (i.p, 1 mg/mouse) without insulin supplement (A) (n = 23) or with DMSO (B) (n = 10). Blood glucose was measured by ACCU-CHECK 2–3 times weekly. Sustainable euglycemia was observed for several months after drug withdrawal while DMSO treated mice expired within 2–4 week after disease onset. The average blood glucose at the disease onset in the cured NOD mice was 314.43 mg/d (Max = 374; Min = 277 mg/dl) versus 384.58 mg/dl (Max = 478, Min = 335 mg/dl) in mice that AG490 failed to restore euglycemia (p,0.0014). An average blood glucose in cured NOD mice treated with AG490 was 169.82 mg/dl623.21, n = 7 versus 555.13663.79, n = 17 in uncured NOD mice (p = 1.15E-11). (C) Diabetes was induced by STZ injection in male BALB/c mice and one week after the last injection diabetic mice were treated with either AG490 or DMSO (D) (n = 5/group). The blood glucose level was significantly lower (p,0.004) in AG490 treated mice when compared with DMSO treated mice. [This figure is intended to be in color online and black and white in print.] doi:10.1371/journal.pone.0036079.g002 PLoS ONE | www.plosone.org 4 May 2012 | Volume 7 | Issue 5 | e36079