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

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Summary

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.

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Abbreviations

IDDM:

Insulin-dependent diabetes mellitus

IL:

interleukin

TNF:

tumour necrosis factor

IFN:

interferon

FBS:

fetal bovine serum

ATA:

aurintricarboxylic acid

CHX:

cycloheximide

PI:

propidium iodide

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Authors and Affiliations

  1. Second Department of Internal Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565, Osaka, Japan

    H. Iwahashi, T. Hanafusa, H. Nakajima, J. Miyagawa, N. Itoh, K. Tomita, M. Namba, M. Kuwajima & Y. Matsuzawa

  2. Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan

    Y. Eguchi & Y. Tsujimoto

  3. Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Osaka, Japan

    T. Noguchi

  4. Department of Laboratory Medicine, School of Medicine, University of Tokushima, Tokushima, Japan

    M. Kuwajima

  5. Department of Biochemistry, Fukui Medical School, Fukui, Japan

    T. Noguchi

Authors
  1. H. Iwahashi
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  2. T. Hanafusa
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  3. Y. Eguchi
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  4. H. Nakajima
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  5. J. Miyagawa
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  6. N. Itoh
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  7. K. Tomita
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  8. M. Namba
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  9. M. Kuwajima
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  10. T. Noguchi
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  11. Y. Tsujimoto
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  12. Y. Matsuzawa
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Iwahashi, H., Hanafusa, T., Eguchi, Y. et al. Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2. Diabetologia 39, 530–536 (1996). https://doi.org/10.1007/BF00403299

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  • DOI: https://doi.org/10.1007/BF00403299

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