The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus

Lenzen, Sigurd; Tiedge, Markus; Elsner, Matthias; Lortz, Stephan; Weiß, H.; Jörns, Anne; Klöppel, Günter; Wedekind, Dirk; Prokop, C.‐M.; Hedrich, Hans J.

doi:10.1007/s001250100625

Cited by 115 publications

(132 citation statements)

References 23 publications

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“…The following antibodies were used for flow cytometry: CD4 (OX-38) FITC, CD3 (G4.18) PE, (BD, Heidelberg, Germany); CD8 (OX-8) FITC, CD8 (OX-8) PE, TCR (R73) FITC, CD45RA (OX-33) FITC, NKR (10/78) FITC, ED1 FITC (all from Serotec, Düsseldorf, Germany). To determine the regulatory and auto-aggressive potential, two different adoptive transfer protocols were used: (1) …”

Section: Methodsmentioning

confidence: 99%

“…In contrast to other established rodent models such as the biobreeding diabetesprone (BB-DP) rat and the NOD mouse, it develops the diabetic syndrome without lymphopenia or without an immune defect in the natural killer (NK)/T-lymphocyte population [1].…”

Section: Introductionmentioning

confidence: 92%

“…Morphology of pancreas, pancreas-draining peripheral lymph nodes and spleen Pancreas and the secondary lymphoid organs were removed, fixed and immunostained by the avidin-biotin complex method or fluorescence method by light microscopy as previously described [1]. The following polyclonal and monoclonal antibodies were used to identify the beta cells and immune cells: rat insulin TGF-β2 (Santa Cruz Biotechnology, Santa Cruz, CA, USA); and the forkhead box protein 3 (FOXP3) antibody (Natutec, Frankfurt, Germany).…”

Section: Cells)mentioning

confidence: 99%

“…The LEW.1AR1-iddm (IDDM) rat is an animal model of autoimmune diabetes [1] with characteristics closely resembling human type 1 diabetes [2]. In contrast to other established rodent models such as the biobreeding diabetesprone (BB-DP) rat and the NOD mouse, it develops the diabetic syndrome without lymphopenia or without an immune defect in the natural killer (NK)/T-lymphocyte population [1].…”

Section: Introductionmentioning

confidence: 99%

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Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

et al. 2009

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Aims/hypothesis The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes. Methods CD4 + or CD8 + T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn rnu or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes. Results After adoptive transfer of CD4 + T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn rnu rats, 50% of the recipients developed diabetes. Transfer of CD8 + T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after cotransfer of CD4 + and CD8 + T cells. Adoptive transfer of CD8 + T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8 + /CD25 + and CD4 + /CD25 + T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabetic rats. Conclusions/interpretation Our results show that adoptive transfer of CD4 + but not CD8 + T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8 + T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8 + T cells may have beneficial effects in the control of beta cell autoimmunity. Keywords

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Cells)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

et al. 2009

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“…Thin sections were stained using the post-embedding method of immunogold for insulin (1:200-1:500; A565; DAKO, Hamburg, Germany) and IL-1β (1:50-1:400; Serotec, Oxford, UK) to localise these proteins by electron microscopy (EM 10; Zeiss, Oberkochem, Germany) in the subcellular compartments of pancreatic beta cells and immune cells [15].…”

Section: Immunogold Stainingmentioning

confidence: 99%

Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated

2006

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Aims/hypothesis It has recently been proposed that IL-1β may be responsible for beta cell death in type 2 diabetes mellitus. Major support for this assumption was derived from experiments in the gerbil Psammomys obesus (sand rat), a model for nutritionally induced non-insulin-dependent type 2 diabetes. Using gerbil-specific primers for the analysis of gene expression, we investigated the validity of this hypothesis. Methods Gene expression was analysed by real-time RT-PCR of isolated and laser-microdissected islets and by in situ RT-PCR, both in beta cells and in immune cells, as well as in lymph nodes and spleen. Results We were unable to detect Il-1β and the IL-1β-inducible enzyme inducible nitric oxide synthase (iNos) by in situ RT-PCR, either in the pancreatic beta cells, or in the small number of non-activated immune cells of healthy and diabetic Psammomys obesus after 1 and 3 weeks on a highenergy diet. Very low levels of Il-1β and iNos mRNA were detectable in collagenase-isolated and laser-microdissected islets of normoglycaemic gerbils by real-time RT-PCR without any increase of these mRNAs in islets from diabetic animals. These results were confirmed by electron microscopy with immunogold staining for IL-1β and insulin. Conclusions/interpretation The diabetic syndrome induced in Psammomys obesus by high-energy diet is a classical type 2 diabetes model, which does not show any evidence of an involvement of the proinflammatory cytokine IL-1β or of activated immune cells in its pathogenesis. This is clearly at variance with the situation in type 1 diabetes.

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Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Janapati,

Junapudi

2024

Anim Models and Exp Med

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Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by hyperglycemia, a condition involving a high blood glucose level brought on by deficiencies in insulin secretion, decreased activity of insulin, or both. Prolonged effects of diabetes include cardiovascular problems, retinopathy, neuropathy, nephropathy, and vascular alterations in both macro‐ and micro‐blood vessels. In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis, identifying targets, and reviewing novel treatment options and medications. Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences. The most popular in vivo studies involves the small animal models, such as rodent models, chemically induced diabetogens like streptozotocin and alloxan, and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals. Other models include virally induced models, diet/nutrition induced diabetic animals, surgically induced models or pancreatectomy models, and non‐obese models. Large animals or non‐rodent models like porcine (pig), canine (dog), nonhuman primate, and Zebrafish models are also outlined. The in vitro models discussed are murine and human beta‐cell lines and pancreatic islets, human stem cells, and organoid cultures. The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition of α‐glucosidase activity.

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The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus

Abstract: This Type I diabetic rat develops a spontaneous insulin-dependent autoimmune diabetes through beta cell apoptosis. It could prove to be a valuable new animal model for clarifying the mechanisms involved in the development of autoimmune diabetes.

Cited by 115 publications

References 23 publications

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

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