The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells
Open accessAbstract
The use of embryonic stem cells for cell-replacement therapy in diseases like diabetes mellitus requires methods to control the development of multipotent cells. We report that treatment of mouse embryonic stem cells with inhibitors of phosphoinositide 3-kinase, an essential intracellular signaling regulator, produced cells that resembled pancreatic β cells in several ways. These cells aggregated in structures similar, but not identical, to pancreatic islets of Langerhans, produced insulin at levels far greater than previously reported, and displayed glucose-dependent insulin release in vitro . Transplantation of these cell aggregates increased circulating insulin levels, reduced weight loss, improved glycemic control, and completely rescued survival in mice with diabetes mellitus. Graft removal resulted in rapid relapse and death. Graft analysis revealed that transplanted insulin-producing cells remained differentiated, enlarged, and did not form detectable tumors. These results provide evidence that embryonic stem cells can serve as the source of insulin-producing replacement tissue in an experimental model of diabetes mellitus. Strategies for producing cells that can replace islet functions described here can be adapted for similar uses with human cells.
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Cites
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326
The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R. J., & Wright, C. V. E. (2002) · Nature Genetics · doi:10.1038/ng959 · Cited by 1,007
Rane, S. G., Dubus, P., Mettus, R. V., Galbreath, E. J., Boden, G., Reddy, E. P., & Barbacid, M. (1999) · Nature Genetics · doi:10.1038/8751 · Cited by 700
Cited by
Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., & Brivanlou, A. H. (2004) · Nature Medicine · doi:10.1038/nm979 · Cited by 2,109
WNT and β-catenin signalling: diseases and therapies
Moon, R. T., Kohn, A. D., Ferrari, G. V. D., & Kaykas, A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1427 · Cited by 1,763
Duan, F. F., Liu, J. H., & March, J. C. (2015) · Diabetes · doi:10.2337/db14-0635 · Cited by 263
Global expression analysis of gene regulatory pathways during endocrine pancreatic development
Gu, G., Wells, J. M., Dombkowski, D., Preffer, F., Aronow, B., & Melton, D. A. (2004) · Development · doi:10.1242/dev.00921 · Cited by 229
Artifactual Insulin Release From Differentiated Embryonic Stem Cells
Hansson, M., Tonning, A., Frandsen, U., Petri, A., Rajagopal, J., Englund, M. C. O., Heller, R. S., Håkansson, J., Fleckner, J., Sköld, H. N., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.10.2603 · Cited by 225
Metadata
- Authors
- Hori, Y., Rulifson, I. C., Tsai, B. C., Heit, J. J., Cahoy, J. D., & Kim, S. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-11-19
- Volume
- 99
- Issue
- 25
- Pages
- 16105-16110
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2046703988
- Cited by
- 421
- References
- 3
- FWCI
- 40.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Hori, Y., Rulifson, I. C., Tsai, B. C., Heit, J. J., Cahoy, J. D., & Kim, S. K. (2002). Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.252618999
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