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Diabetologia
Published in: Diabetologia 3/2014

01-03-2014 | Article

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

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

Published in: Diabetologia | Issue 3/2014

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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.
Appendix
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Metadata
Title
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
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
Publication date
01-03-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 3/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3125-4

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