Fasting-mimicking diet promotes Ngn3-driven β-cell regeneration to reverse diabetes

• Chia-Wei Cheng ^[1] ; Valentina Villani ^[1] ; Roberta Buono ^[1]
  1. [1] University of Southern California

     University of Southern California

     Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 168, Nº. 5, 2017, págs. 775-788
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.