Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene

Kenichi Matsushita, Hajime Okita, Atsushi Suzuki, Kouji Shimoda, Mariko Fukuma, Taketo Yamada, Fumihiko Urano, Takahiro Honda, Makoto Sano, Shiro Iwanaga, Satoshi Ogawa, Jun Ichi Hata, Akihiro Umezawa

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9 Citations (Scopus)

Abstract

EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1α promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 - possible heterodimeric partners for EAT in the anti-apoptotic process - were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic β cells. EAT may inhibit apoptosis of β cells, allowing these cells to circumvent the process of apoptosis until the adult stage.

Original languageEnglish
Pages (from-to)105-116
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume203
Issue number1-2
DOIs
Publication statusPublished - 2003 May 30

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Keywords

  • Apoptosis
  • EAT
  • Islet β-cell
  • Transgenic mice
  • mcl-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Matsushita, K., Okita, H., Suzuki, A., Shimoda, K., Fukuma, M., Yamada, T., Urano, F., Honda, T., Sano, M., Iwanaga, S., Ogawa, S., Hata, J. I., & Umezawa, A. (2003). Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene. Molecular and Cellular Endocrinology, 203(1-2), 105-116. https://doi.org/10.1016/S0303-7207(03)00095-9