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Yoko Yagishita, Akira Uruno, Dionysios V Chartoumpekis, Thomas W Kensler, and Masayuki Yamamoto

reflect immune system dysregulation ( Van Belle et al . 2009 ). Therefore, studies utilizing alternative models to address the roles of Nrf2 signaling in autoimmune-based diabetes are needed. Non-obese diabetic (NOD) mice have been used widely as a

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Ke Ke, Ok-Joo Sul, Soo-Wol Chung, Jae-Hee Suh, and Hye-Seon Choi

loss by amplifying RANKL-induced signaling in OCs. Materials and methods Animals and study design Nod2 − / − ( Nod2 -knockout (KO)) mice were purchased from the Jackson Laboratory. The mice were bred with C57BL/6J mice and maintained by

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Elizabeth S Barrie, Mels Lodder, Paul H Weinreb, Jill Buss, Amer Rajab, Christopher Adin, Qing-Sheng Mi, and Gregg A Hadley

Introduction Type 1 diabetes is a T cell-mediated autoimmune disease caused by the destruction of insulin-producing β cells of the islets of Langerhans in the pancreas, resulting in a hyperglycemic state. Non-obese diabetic (NOD) mice (NOD

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Astrid Chamson-Reig, Edith J Arany, Kelly Summers, and David J Hill

NOD mouse and BioBreeding (BB) rat ( Lefebvre et al . 2006 ). However, food antigens can also interact with the gut immune system, resulting in a Th1 cytokine pattern of expression within the Peyer's patches of young NOD mice ( Chakir et al . 2005

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Jacob Jelsing, Niels Vrang, Søren B van Witteloostuijn, Michael Mark, and Thomas Klein

as add-on therapy to insulin in reducing BG levels in a small sample of patients with T1D. In addition, sitagliptin was shown to preserve islet transplants in non-obese diabetic (NOD) mice ( Kim et al . 2009 , 2010 ). This mouse model spontaneously

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Jane A Mitchell, Mark J Paul-Clark, Graham W Clarke, Shaun K McMaster, and Neil Cartwright

including NFκB and AP-1. PRRs include transmembrane toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins containing leucine-rich repeats (NLRs). Bacterial LPS and its effects on biological systems

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Jon G Mabley, Pal Pacher, Kanneganti G K Murthy, William Williams, Garry J Southan, Andrew L Salzman, and Csaba Szabo

following sources. Amplex red xanthine/xanthine oxidase assay kits were obtained from Molecular Probes (Eugene, OR, USA). Streptozotocin and sodium citrate were obtained from Sigma. BALB/c and NOD mice were purchased from Taconic (Germantown, NY, USA

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Wenjuan Liu, Harry Kevin Lau, Dong Ok Son, Tianru Jin, Yehong Yang, Zhaoyun Zhang, Yiming Li, Gerald J Prud’homme, and Qinghua Wang

/or decreasing apoptosis. However, comparable studies have not been performed with human islets. To test our hypothesis for the existence of a collaborative effect, we transplanted a suboptimal number of human islets into diabetic immunodeficient NOD

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Guofeng Zhang, Hiroki Hirai, Tao Cai, Junnosuke Miura, Ping Yu, Hanxia Huang, Martin R Schiller, William D Swaim, Richard D Leapman, and Abner L Notkins

was increased at 60 min, was highest at 90 min (Fig. 4D ), and decreased thereafter (not shown). RESP18 protein also was increased in the islets of NOD mice following the development of diabetes. Western blots showed a tenfold increase at 2 days after

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J Sternesjo and S Sandler

Administration of the T-helper 1 (Th 1) cell promoting cytokine interleukin-12 (IL-12) accelerates the development of autoimmune diabetes in non-obese diabetic (NOD) mice. In this study we examined the effects of IL-12 on isolated islets from NMRI (Naval Medical Research Institute-established) mice, Sprague-Dawley (S-D) rats and NOD mice. NMRI and S-D islets were cultured in medium RPMI 1640 + 10% fetal calf serum and exposed for 48 h to recombinant mouse IL-12 (0, 0.1, 1 and 10 ng/ml). Islet glucose metabolism, as measured by glucose oxidation rate, was suppressed by about 25% in NMRI islets exposed to 10 ng/ml IL-12. In rat islets 0.1 ng/ml IL-12 induced a 20% decrease in glucose oxidation rate. Islets cultured with 10 ng/ml IL-12 showed a decrease in medium insulin accumulation both in mouse and rat. Glucose-stimulated insulin release was lowered in rat islets exposed to 10 ng/ml IL-12, but not affected in NMRI islets. In NMRI islets IL-12 did not influence nitric oxide production as measured by nitrite formation. In rat islets IL-12 induced a decrease in nitrite formation compared with control islets. Islets were isolated from female NOD mice (age 5, 12, 20 and 26 weeks) and examined either immediately or cultured for 7 days with 10 ng/ml IL-12 alone or in combination with 4 ng/ml of the T-cell stimulating cytokine interleukin-2 (IL-2). In the age groups > 5 weeks of age the glucose-stimulated insulin release was lower in freshly isolated compared with cultured control islets. IL-2 + IL-12 addition induced a small decrease in glucose-stimulated insulin release in islets from 12-week-old animals. With increasing age the DNA content in freshly isolated islets increased due to immune cell infiltration. The DNA content in cultured islets was decreased by 40-60% compared with freshly isolated islets in the age groups over 5 weeks. Islet insulin content was similar in both freshly isolated and cultured islets. None of the cytokines, either alone or in combination, affected islet DNA or insulin content. We conclude that IL-12 has minor suppressive effects in vitro on normal rodent islets. It is likely that the reported accelerated diabetes development of IL-12 administration to NOD mice in vivo is not mediated by a direct toxic effect to the islets. The suppressed insulin release in NOD mouse islets treated with IL-2 + IL-12 suggests, however, that the accelerating effect might partly be attributed to stimulation of immune cells present in the insulitic lesion.