Fasting-Mimicking Diet Promotes Ngn3-Driven ß-Cell Regeneration to Reverse Diabetes.
Cell
; 168(5): 775-788.e12, 2017 02 23.
Article
en En
| MEDLINE
| ID: mdl-28235195
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 ß 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. PAPERCLIP.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ayuno
/
Diabetes Mellitus Tipo 1
/
Diabetes Mellitus Tipo 2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article