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

• Main Authors: Villani, Valentina (Author), Buono, Roberta (Author), Wei, Min (Author), Kumar, Sanjeev (Author), Cohen, Pinchas (Author), Sneddon, Julie B. (Author), Perin, Laura (Author), Longo, Valter D. (Author), Cheng, Chia-Wei (Contributor), Yilmaz, Omer (Contributor)
• Other Authors: Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Elsevier BV, 2018-07-23T18:50:49Z.
• Subjects: Article
• Online Access: Get fulltext

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.