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

Research output: Contribution to journalArticle

41 Citations (Scopus)

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

Fingerprint

Transgenic Mice
Islets of Langerhans
Exocrine Pancreas
Neoplasms
Endocrine Cells
Pancreas
Stem Cells
Epithelium
Insulin
Somatostatin-Secreting Cells
Pancreatic Ducts
Adenoma
Cell Count
Epithelial Cells
Apoptosis
Growth

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., ... Itakura, M. (2000). Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6. Diabetologia, 43(3), 332-339.

Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6. / Yamaoka, T.; Yano, M.; Yamada, T.; Matsushita, T.; Moritani, M.; Ii, S.; Yoshimoto, K.; Hata, J.; Itakura, M.

In: Diabetologia, Vol. 43, No. 3, 2000, p. 332-339.

Research output: Contribution to journalArticle

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, vol. 43, no. 3, pp. 332-339.
Yamaoka T, Yano M, Yamada T, Matsushita T, Moritani M, Ii S et al. Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6. Diabetologia. 2000;43(3):332-339.
Yamaoka, T. ; Yano, M. ; Yamada, T. ; Matsushita, T. ; Moritani, M. ; Ii, S. ; Yoshimoto, K. ; Hata, J. ; Itakura, M. / Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6. In: Diabetologia. 2000 ; Vol. 43, No. 3. pp. 332-339.
@article{896c395965704b32bb93c39ebfc4ee82,
title = "Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6",
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.",
keywords = "Cell differentiation, Diabetes mellitus, Embryology, Islets of Langerhans, Transcription factors",
author = "T. Yamaoka and M. Yano and T. Yamada and T. Matsushita and M. Moritani and S. Ii and K. Yoshimoto and J. Hata and M. Itakura",
year = "2000",
language = "English",
volume = "43",
pages = "332--339",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Diabetes and pancreatic tumours in transgenic mice expressing Pa x 6

AU - Yamaoka, T.

AU - Yano, M.

AU - Yamada, T.

AU - Matsushita, T.

AU - Moritani, M.

AU - Ii, S.

AU - Yoshimoto, K.

AU - Hata, J.

AU - Itakura, M.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Cell differentiation

KW - Diabetes mellitus

KW - Embryology

KW - Islets of Langerhans

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=2142856418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2142856418&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 332

EP - 339

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 3

ER -