d with either 25 or 50 mg/kg ISO-092 or Animals Animals were group housed in polycarbonate cages with wire lids and filter covers during study except for when a single animal remained in a group or during postoperative recovery, provided autoclaved 7012 or irradiated 5LG4 diet and filtered tap water or spring water acidified to a pH of 2.5-3.5 ad libitum. BBDP and MAD rat colonies at BRM were housed on conventional racks within a VAF barrier facility and either continued to be housed as such once enrolled onto study or were transferred to negative-pressure isolators in a separate nonbarrier facility. Female NOD mice were purchased from The Jackson Laboratory at 6 week of age and housed in a dedicated room on ventilated racks within a VAF barrier facility. All animals were observed daily for signs of toxicity such as changes in respiration, changes in motor activity, convulsions, changes in reflexes, cardiovascular signs, piloerection, lethargy and gastrointestinal upset. Any unthrift animal was examined by the study director and/or veterinarian. If the animal appeared to be in unrelieved pain or distress, the animal was euthanized and a necropsy was GSK126 price performed evaluating gross organ size, color and appearance. Atypical findings were sampled and 3 Efficacy Testing in Rodent Models of T1D vehicle by oral gavage once daily for 14 days. NOD mice were monitored for diabetes onset twice weekly until 25 weeks of age. Mice were euthanized within two days of diabetes onset or at completion of study. 4) For GTT late prevention studies with NOD mice, female mice were 
aged up to 10-12 weeks of age, when once weekly non-fasted blood glucose measurements were initiated to exclude diabetic mice. Non-diabetic mice with blood glucose levels at 14 weeks of age were administered a single IPGTT and mice exhibiting a blood glucose level > 200 mg/dL at either 30 or 60 minutes post challenge and a non-fasted blood glucose level of < 250 mg/dL on Day 1 were assigned to groups and administered the following: 25 mg/kg ISO-092 or vehicle by oral gavage once daily for 14 days; 2 mg/mouse Aralast NP or vehicle by IP injection on Days 1, 4, 7, 10, and 13; or 25 mg/kg Celastrol or vehicle by oral gavage three times weekly. NOD mice were monitored for diabetes onset twice weekly for up to 90 days. Mice were euthanized within two days of diabetes onset or at completion of study. 5) For reversal studies with NOD mice, female mice were aged up to 10 weeks of age, when once weekly non-fasted blood glucose measurements were initiated to exclude diabetic mice. Beginning at 12 weeks of age until 20 weeks of age, nonfasted blood glucose levels were measured three times weekly and diabetic mice were enrolled into groups in a staggered fashion on the same day as confirmation of diabetes onset, and administered the following: 50 g antiCD3 F2 or Hamster IgG F2 isotype control once daily on Days 1-5 by IP injection 1 mg/kg PGCGLP-1 or PGC control once weekly 20590636 by SC injection. For these studies the entry criteria was set at blood glucose levels equaling 250-399 mg/dL on two consecutive readings. 23551948 Mice were euthanized at completion of study or upon reaching a humane end point. Jackson Laboratory, Bar Harbor, was undergoing some construction and during that time T1D incidence in their colony was reduced compared to the incidence at the BRM facility. Similarly, in 2010, T1D incidence was reduced at BRM and this also coincided with local construction activities. Management of glycemic con