Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes
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; ... Show more Show less
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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.
Date issued
2017-02Department
Koch Institute for Integrative Cancer Research at MITJournal
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
ISSN
0092-8674
1097-4172