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

Mol Cell Endocrinol. 2003 May 30;203(1-2):105-16. doi: 10.1016/s0303-7207(03)00095-9.

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 EF1 alpha 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 beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Islet Cell / pathology
  • Animals
  • Apoptosis
  • Cell Size
  • Genes, bcl-2
  • Humans
  • Hyperplasia / etiology*
  • Hyperplasia / pathology
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Liver / pathology
  • Mice
  • Mice, Transgenic
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2*

Substances

  • Insulin
  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2