Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6

T. Yamaoka, M. Yano, T. Yamada, T. Matsushita, M. Moritani, S. Ii, K. Yoshimoto, J. Hata, M. Itakura

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Abstract

Aims/hypothesis. Both endocrine and exocrine cells of the pancreas differentiate from epithelial cells of primitive pancreatic ducts, and four types of pancreatic islet cells (alpha, beta, delta, and PP cells) are derived from the common pluripotent precursor cells. Although Pa x 6 is expressed in all islet cells, Pa x 4 is detected only in beta cells. In homozygous Pa x 4-null mice, beta cells are absent, whereas the number of alpha cells is increased. Therefore, we hypothesized that the balance of Pa x 4 and 6 is one of the determinants by which the common progenitor cells differentiate into alpha or beta cells. Methods. To change this balance, we generated transgenic mice overexpressing Pa x 6 driven by the insulin promoter or the PDX1 promoter. Results. In both types of transgenic mice, normal development of beta cells was disturbed, resulting in apoptosis of beta cells and diabetes. In Insulin/Pa x 6-Tg mice, beta cells were specifically affected, whereas in PDX/Pa x 6-Tg mice, developmental abnormalities involved the whole pancreas including hypoplasia of the exocrine pancreas. Furthermore, PDX/Pa x 6-Tg mice experienced proliferation of both ductal epithelia and islet cells and subsequent cystic adenoma of the pancreas. Conclusion/interpretation. These findings suggest that Pa x 6 promotes the growth of ductal epithelia and endocrine progenitor cells and that the suppression of Pa x 6 is necessary for the normal development of beta cells and the exocrine pancreas.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalDiabetologia
Volume43
Issue number3
Publication statusPublished - 2000

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Keywords

  • Cell differentiation
  • Diabetes mellitus
  • Embryology
  • Islets of Langerhans
  • Transcription factors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Yamaoka, T., Yano, M., Yamada, T., Matsushita, T., Moritani, M., Ii, S., Yoshimoto, K., Hata, J., & Itakura, M. (2000). Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6. Diabetologia, 43(3), 332-339.