caa a22 4500 475771877 CHVBK 20180406123619.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s001250050051 doi (NATIONALLICENCE)springer-10.1007/s001250050051 Diabetes and pancreatic tumours in transgenic mice expressing Pa × 6 [Elektronische Daten] [T. Yamaoka, M. Yano, T. Yamada, T. Matsushita, M. Moritani, S. Ii, K. Yoshimoto, J. Hata, M. Itakura] 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 × 6 is expressed in all islet cells, Pa × 4 is detected only in beta cells. In homozygous Pa × 4-null mice, beta cells are absent, whereas the number of alpha cells is increased. Therefore, we hypothesized that the balance of Pa × 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 × 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 × 6-Tg mice, beta cells were specifically affected, whereas in PDX/Pa × 6-Tg mice, developmental abnormalities involved the whole pancreas including hypoplasia of the exocrine pancreas. Furthermore, PDX/Pa × 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 × 6 promotes the growth of ductal epithelia and endocrine progenitor cells and that the suppression of Pa × 6 is necessary for the normal development of beta cells and the exocrine pancreas. [Diabetologia (2000) 43: 332-339] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetes mellitus, islets of Langerhans, embryology, cell differentiation, transcription factors nationallicence Yamaoka T. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Yano M. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Yamada T. Department of Pathology, Keio University, School of Medicine, Tokyo, Japan, JP aut Matsushita T. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Moritani M. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Ii S. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Yoshimoto K. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut Hata J. Department of Pathology, Keio University, School of Medicine, Tokyo, Japan, JP aut Itakura M. Division of Genetic Information, Institute for Genome Research, The University of Tokushima, Japan, JP aut https://doi.org/10.1007/s001250050051 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050051 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamaoka T. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Yano M. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Yamada T. Department of Pathology, Keio University, School of Medicine, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Matsushita T. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Moritani M. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Ii S. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Yoshimoto K. Otsuka Department of Molecular Nutrition, School of Medicine, The University of Tokushima, Japan, JP aut NATIONALLICENCE 700 1- Hata J. Department of Pathology, Keio University, School of Medicine, Tokyo, Japan, JP aut NATIONALLICENCE 700 1- Itakura M. Division of Genetic Information, Institute for Genome Research, The University of Tokushima, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer