Wnt signaling regulates pancreatic β cell proliferation
| Autor: | Derk ten Berge, Makoto Mark Taketo, Hainan Chen, Matthias Hebrok, Patrick W. Heiser, Seung K. Kim, Xueying Gu, Roel Nusse, Satyajit K. Karnik, Ingrid C. Rulifson |
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| Rok vydání: | 2007 |
| Předmět: |
Cell
Biology Wnt3 Protein Mice Cyclin D2 Cyclins Insulin-Secreting Cells Wnt3A Protein medicine Animals Cell Proliferation Homeodomain Proteins geography Multidisciplinary geography.geographical_feature_category Cell growth Wnt signaling pathway LRP5 Biological Sciences Islet Immunohistochemistry Mice Mutant Strains Cell biology Wnt Proteins medicine.anatomical_structure Cancer research Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 104:6247-6252 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0701509104 |
| Popis: | There is widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet cells. Wnt signaling is an important regulator of organ growth and cell fates, and genes encoding Wnt-signaling factors are expressed in the pancreas. However, it is unclear whether Wnt signaling regulates pancreatic islet proliferation and differentiation. Here we provide evidence that Wnt signaling stimulates islet β cell proliferation. The addition of purified Wnt3a protein to cultured β cells or islets promoted expression of Pitx2, a direct target of Wnt signaling, and Cyclin D2, an essential regulator of β cell cycle progression, and led to increased β cell proliferation in vitro . Conditional pancreatic β cell expression of activated β-catenin, a crucial Wnt signal transduction protein, produced similar phenotypes in vivo , leading to β cell expansion, increased insulin production and serum levels, and enhanced glucose handling. Conditional β cell expression of Axin, a potent negative regulator of Wnt signaling, led to reduced Pitx2 and Cyclin D2 expression by β cells, resulting in reduced neonatal β cell expansion and mass and impaired glucose tolerance. Thus, Wnt signaling is both necessary and sufficient for islet β cell proliferation, and our study provides previously unrecognized evidence of a mechanism governing endocrine pancreas growth and function. |
| Databáze: | OpenAIRE |
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