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

• Published in: Diabetologia 2014-03, Vol.57 (3), p.512-521
• Main Authors: Jörns, Anne, Arndt, Tanja, zu Vilsendorf, Andreas Meyer, Klempnauer, Jürgen, Wedekind, Dirk, Hedrich, Hans-Jürgen, Marselli, Lorella, Marchetti, Piero, Harada, Nagakatsu, Nakaya, Yutaka, Wang, Gen-Sheng, Scott, Fraser W., Gysemans, Conny, Mathieu, Chantal, Lenzen, Sigurd
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Cell death; Cytokines; Cytokines - metabolism; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Expression Regulation; Human Physiology; Humans; Immunohistochemistry; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Interferon-gamma - metabolism; Internal Medicine; Laboratory animals; Medical schools; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred NOD; Pancreas; Pathogenesis; Rats; Rats, Inbred BB; Rats, Inbred Lew; Real-Time Polymerase Chain Reaction; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-013-3125-4

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.