, Volume 39, Issue 5, pp 530–536 | Cite as

Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2

  • H. Iwahashi
  • T. Hanafusa
  • Y. Eguchi
  • H. Nakajima
  • J. Miyagawa
  • N. Itoh
  • K. Tomita
  • M. Namba
  • M. Kuwajima
  • T. Noguchi
  • Y. Tsujimoto
  • Y. Matsuzawa


Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1Β, tumour necrosis factor-α, and interferon-γ) induced apoptotic cell death in the mouse pancreatic beta-cell line ΒTC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line αTC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in ΒTC1 cells. The abundance of endogenous Bcl-2 in ΒTC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in ΒTC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.


Pancreatic beta cell Bcl-2 apoptosis cytokine interleukin-1 tumour necrosis factor interferon-γ 



Insulin-dependent diabetes mellitus




tumour necrosis factor




fetal bovine serum


aurintricarboxylic acid




propidium iodide


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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Iwahashi
    • 1
  • T. Hanafusa
    • 1
  • Y. Eguchi
    • 2
  • H. Nakajima
    • 1
  • J. Miyagawa
    • 1
  • N. Itoh
    • 1
  • K. Tomita
    • 1
  • M. Namba
    • 1
  • M. Kuwajima
    • 1
    • 4
  • T. Noguchi
    • 3
    • 5
  • Y. Tsujimoto
    • 2
  • Y. Matsuzawa
    • 1
  1. 1.Second Department of Internal MedicineOsaka University Medical SchoolOsakaJapan
  2. 2.Department of Medical Genetics, Biomedical Research CenterOsaka University Medical SchoolOsakaJapan
  3. 3.Department of Nutrition and Physiological ChemistryOsaka University Medical SchoolOsakaJapan
  4. 4.Department of Laboratory Medicine, School of MedicineUniversity of TokushimaTokushimaJapan
  5. 5.Department of BiochemistryFukui Medical SchoolFukuiJapan

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