Diabetologia

, Volume 57, Issue 3, pp 512–521 | Cite as

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

  • 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
Article

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.

Keywords

Animal models Cytokines Human Immune cells Pancreatic islets Type 1 diabetes 

Abbreviations

BB

BioBreeding

DIG

Digoxigenin

FoxP3

Forkhead box P3

iNOS

Inducible nitric oxide synthase

NFκB

Nuclear factor κB

TGF-β1

Transforming growth factor β1

Supplementary material

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ESM Table 7(PDF 161 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Anne Jörns
    • 1
    • 2
  • Tanja Arndt
    • 1
  • Andreas Meyer zu Vilsendorf
    • 3
  • Jürgen Klempnauer
    • 3
  • Dirk Wedekind
    • 4
  • Hans-Jürgen Hedrich
    • 4
  • Lorella Marselli
    • 5
  • Piero Marchetti
    • 5
  • Nagakatsu Harada
    • 6
  • Yutaka Nakaya
    • 6
  • Gen-Sheng Wang
    • 7
  • Fraser W. Scott
    • 7
  • Conny Gysemans
    • 8
  • Chantal Mathieu
    • 8
  • Sigurd Lenzen
    • 1
  1. 1.Institute of Clinical BiochemistryHannover Medical SchoolHannoverGermany
  2. 2.Centre of AnatomyHannover Medical SchoolHannoverGermany
  3. 3.Department of General, Visceral and Transplantation SurgeryHannover Medical SchoolHannoverGermany
  4. 4.Institute of Laboratory Animal ScienceHannover Medical SchoolHannoverGermany
  5. 5.Islet Cell Laboratory, Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  6. 6.Institute of Health Biosciences, Department of Nutrition and MetabolismUniversity of Tokushima Graduate SchoolTokushimaJapan
  7. 7.Chronic Disease ProgramOttawa Hospital Research InstituteOttawaCanada
  8. 8.Clinical and Experimental EndocrinologyCatholic University of LeuvenLeuvenBelgium

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