Fasting-Mimicking Diet Promotes Ngn3-Driven Beta-Cell Regeneration to Reverse Diabetes

Publication

Cell

Author(s)

Chia-Wei Cheng, Valentina Villani, Roberta Buono, Min Wei, Sanjeev Kumar, Omer H. Yilmaz, Pinchas Cohen, Julie B. Sneddon, Laura Perin, and Valter D. Longo

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 b 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

February 23, 2017

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