Islet infiltration,cytokine expression and beta cell death in the NOD mouse,BB rat,Komeda rat,LEW.1AR1-iddm rat and humans with type 1 diabetes |
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Authors: | Anne Jörns Tanja Arndt Andreas Meyer zu Vilsendorf Jürgen Klempnauer Dirk Wedekind Hans-Jürgen Hedrich Lorella Marselli Piero Marchetti Nagakatsu Harada Yutaka Nakaya Gen-Sheng Wang Fraser W Scott Conny Gysemans Chantal Mathieu Sigurd Lenzen |
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Institution: | 1. Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany 2. Centre of Anatomy, Hannover Medical School, Hannover, Germany 3. Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany 4. Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany 5. Islet Cell Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy 6. Institute of Health Biosciences, Department of Nutrition and Metabolism, University of Tokushima Graduate School, Tokushima, Japan 7. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada 8. Clinical and Experimental Endocrinology, Catholic University of Leuven, Leuven, Belgium
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Abstract: | Aims/hypothesis Research on the pathogenesis of type 1 diabetes relies heavily on good animal models. The aim of this work was to study the translational value of animal models of type 1 diabetes to the human situation. Methods We compared the four major animal models of spontaneous type 1 diabetes, namely the NOD mouse, BioBreeding (BB) rat, Komeda rat and LEW.1AR1-iddm rat, by examining the immunohistochemistry and in situ RT-PCR of immune cell infiltrate and cytokine pattern in pancreatic islets, and by comparing findings with human data. Results After type 1 diabetes manifestation CD8+ T cells, CD68+ macrophages and CD4+ T cells were observed as the main immune cell types with declining frequency, in infiltrated islets of all diabetic pancreases. IL-1β and TNF-α were the main proinflammatory cytokines in the immune cell infiltrate in NOD mice, BB rats and LEW.1AR1-iddm rats, as well as in humans. The Komeda rat was the exception, with IFN-γ and TNF-α being the main cytokines. In addition, IL-17 and IL-6 and the anti-inflammatory cytokines IL-4, IL-10 and IL-13 were found in some infiltrating immune cells. Apoptotic as well as proliferating beta cells were observed in infiltrated islets. In healthy pancreases no proinflammatory cytokine expression was observed. Conclusions/interpretation With the exception of the Komeda rat, the animal models mirror very well the situation in humans with type 1 diabetes. Thus animal models of type 1 diabetes can provide meaningful information on the disease processes in the pancreas of patients with type 1 diabetes. |
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