The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Wnt signaling regulates pancreatic β cell proliferation
Open accessAbstract
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.
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Cites
The Wnt Signaling Pathway in Development and Disease
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Self-citationβ-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011
Wnt proteins are lipid-modified and can act as stem cell growth factors
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Self-citationInsulin-promoter-factor 1 is required for pancreas development in mice
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Five-Year Follow-Up After Clinical Islet Transplantation
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PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
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Marcheva, B., Ramsey, K. M., Buhr, E. D., Kobayashi, Y., Su, H., Ko, C. H., Ivanova, G., Omura, C., Mo, S., Vitaterna, M. H., et al. (2010) · Nature · doi:10.1038/nature09253 · Cited by 1,525
Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes
Lyssenko, V., Lupi, R., Marchetti, P., Del Guerra, S., Orho-Melander, M., Almgren, P., Sjögren, M., Ling, C., Eriksson, K.-F., Lethagen, Υ.-L., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30706 · Cited by 829
Grigoryan, T., Wend, P., Klaus, A., & Birchmeier, W. (2008) · Genes & Development · doi:10.1101/gad.1686208 · Cited by 560
Developmental biology of the pancreas: A comprehensive review
Gittes, G. K. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2008.10.024 · Cited by 451
Chen, H., Gu, X., Su, I.-H., Bottino, R., Contreras, J. L., Tarakhovsky, A., & Kim, S. K. (2009) · Genes & Development · doi:10.1101/gad.1742509 · Cited by 366
Self-citation
Metadata
- Authors
- Rulifson, I. C., Karnik, S. K., Heiser, P. W., ten Berge, D., Chen, H., Gu, X., Taketo, M. M., Nusse, R., Hebrok, M., & Kim, S. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-04-10
- Volume
- 104
- Issue
- 15
- Pages
- 6247-6252
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2058276161
- Cited by
- 342
- References
- 46
- FWCI
- 28.44
- Type
- journal article
- Language
- en
- Open access
- green
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- Rulifson, I. C., Karnik, S. K., Heiser, P. W., ten Berge, D., Chen, H., Gu, X., Taketo, M. M., Nusse, R., Hebrok, M., & Kim, S. K. (2007). Wnt signaling regulates pancreatic β cell proliferation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0701509104
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