The DOI matches its OpenAlex record; 40 of the 40 references it cites were found in a registry or an index.
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth
Open accessAbstract
Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing beta cells. The mechanisms governing replication of terminally differentiated beta cells and neogenesis from progenitor cells are unclear. Mice lacking insulin receptor substrate-2 (Irs2) develop beta cell failure, suggesting that insulin signaling is required to maintain an adequate beta cell mass. We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts.
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Cites
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
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Self-citationInsulin signalling and the regulation of glucose and lipid metabolism
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Cited by
Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure
Talchai, C., Xuan, S., Lin, H. V., Sussel, L., & Accili, D. (2012) · Cell · doi:10.1016/j.cell.2012.07.029 · Cited by 1,415
Self-citation(2004) · doi:10.1016/s0092-8674(04)00452-0 · Cited by 1,356
Self-citationGlucolipotoxicity: fuel excess and β-cell dysfunction
Poitout, V., & Robertson, R. P. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0023 · Cited by 1,092
The role of incretins in glucose homeostasis and diabetes treatment
Kim, W., & Egan, J. M. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.000604 · Cited by 824
Biochemical and cellular properties of insulin receptor signalling
Haeusler, R. A., McGraw, T. E., & Accili, D. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.89 · Cited by 739
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Metadata
- Authors
- Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs, W., Wright, C. V. E., White, M. F., Arden, K. C., & Accili, D.
- Venue
- Journal of Clinical Investigation
- Publisher
- American Society for Clinical Investigation
- Published
- 2002-12-15
- Volume
- 110
- Issue
- 12
- Pages
- 1839-1847
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2064417575
- Cited by
- 580
- References
- 40
- FWCI
- 21.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs, W., Wright, C. V. E., White, M. F., Arden, K. C., & Accili, D. (2002). The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth. Journal of Clinical Investigation. https://doi.org/10.1172/jci16857
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
