Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

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Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

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Title: Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway
Author: Blum, Barak; Roose, Adam N; Barrandon, Ornella; Maehr, René; Arvanites, Anthony C; Davidow, Lance S; Davis, Jeffrey C; Peterson, Quinn P; Rubin, Lee L; Melton, Douglas A

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Citation: Blum, Barak, Adam N Roose, Ornella Barrandon, René Maehr, Anthony C Arvanites, Lance S Davidow, Jeffrey C Davis, Quinn P Peterson, Lee L Rubin, and Douglas A Melton. 2014. “Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway.” eLife 3 (1): e02809. doi:10.7554/eLife.02809. http://dx.doi.org/10.7554/eLife.02809.
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Abstract: Dysfunction or death of pancreatic β cells underlies both types of diabetes. This functional decline begins with β cell stress and de-differentiation. Current drugs for type 2 diabetes (T2D) lower blood glucose levels but they do not directly alleviate β cell stress nor prevent, let alone reverse, β cell de-differentiation. We show here that Urocortin 3 (Ucn3), a marker for mature β cells, is down-regulated in the early stages of T2D in mice and when β cells are stressed in vitro. Using an insulin expression-coupled lineage tracer, with Ucn3 as a reporter for the mature β cell state, we screen for factors that reverse β cell de-differentiation. We find that a small molecule inhibitor of TGFβ receptor I (Alk5) protects cells from the loss of key β cell transcription factors and restores a mature β cell identity even after exposure to prolonged and severe diabetes. DOI: http://dx.doi.org/10.7554/eLife.02809.001
Published Version: doi:10.7554/eLife.02809
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204634/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454628
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