Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes
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nihms849263.pdf
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Author(s)
Villani, Valentina
Buono, Roberta
Wei, Min
Kumar, Sanjeev
Cohen, Pinchas
Sneddon, Julie B.
Perin, Laura
Longo, Valter D.
Cheng, Chia-Wei
Yilmaz, Omer
Date Issued
February 2017
Journal
Cell
Publisher
Elsevier BV
Citation
Cheng, Chia-Wei et al. “Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes.” Cell 168, 5 (February 2017): 775–788 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing β cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models. In human type 1 diabetes pancreatic islets, fasting conditions reduce PKA and mTOR activity and induce Sox2 and Ngn3 expression and insulin production. The effects of the FMD are reversed by IGF-1 treatment and recapitulated by PKA and mTOR inhibition. These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
http://dx.doi.org/10.1016/J.CELL.2017.01.040
