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

Diabetologia. 2014 Mar;57(3):512-21. doi: 10.1007/s00125-013-3125-4. Epub 2013 Dec 6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Cytokines / metabolism*
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology*
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred NOD
  • Rats
  • Rats, Inbred BB
  • Rats, Inbred Lew
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma