Apoptosis and remodelling of beta cells by paracrine interferon-γ without insulitis in transgenic mice

T. Yamaoka, M. Yano, C. Idehara, T. Yamada, S. Tomonari, M. Moritani, S. Ii, K. Yoshimoto, J. Hata, M. Itakura

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Abstract

Aims/hypothesis. To examine whether interferon-γ destroys islet beta cells directly or indirectly through lymphocyte activation, or whether direct action of interferon-γ on beta cells by itself induces diabetes without insulitis. Methods. To avoid possible nonspecific breakdown of beta cells by transgenic overexpression of interferon-γ by the insulin promoter, we generated transgenic mice expressing interferon-γ under the control of rat glucagon promoter (RGP-IFN-γ-Tg mice). Results. The absence of insulitis in RGP-IFN-γ-Tg mice enabled us to investigate the direct effects of paracrine interferon-γ. In RGP-IFN-γ-Tg mice, serum concentrations of interferon-γ and tumour necrosis factor-α (TNF-α) were 50 and 6 times higher than those in their littermates, respectively, and glucose-responsive insulin secretion decreased to one-half the level of that in the littermates. Transgenic interferon-γ induced remodelling of beta cells where apoptosis of many beta cells was compensated by their vigorous regeneration and diabetes did not occur in most of the RGP-IFN-γ-Tg mice. Conclusion/interpretation. Interferon-γ alone is insufficient for the complete destruction of beta cells in vivo, and factors other than interferon-γ including activated lymphocytes or other cytokines, are necessary in addition to interferon-γ for the development of Type I (insulin-dependent) diabetes mellitus.

Original languageEnglish
Pages (from-to)566-573
Number of pages8
JournalDiabetologia
Volume42
Issue number5
DOIs
Publication statusPublished - 1999 May 5

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Keywords

  • Apoptosis
  • Insulin secretion
  • Interferon-γ
  • Transgenic mice
  • Tumour necrosis factor
  • Type I diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Yamaoka, T., Yano, M., Idehara, C., Yamada, T., Tomonari, S., Moritani, M., Ii, S., Yoshimoto, K., Hata, J., & Itakura, M. (1999). Apoptosis and remodelling of beta cells by paracrine interferon-γ without insulitis in transgenic mice. Diabetologia, 42(5), 566-573. https://doi.org/10.1007/s001250051196