Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes
2017; Cell Press; Volume: 168; Issue: 5 Linguagem: Inglês
10.1016/j.cell.2017.01.040
ISSN1097-4172
AutoresChia‐Wei Cheng, Valentina Villani, Roberta Buono, Min Wei, Sanjeev Kumar, Ömer Yılmaz, Pinchas Cohen, Julie B. Sneddon, Laura Perin, Valter D. Longo,
Tópico(s)FOXO transcription factor regulation
ResumoStem-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.PaperClip/cms/asset/f90d7b73-e7d3-4ef8-91a9-9bec91d305c3/mmc2.mp3Loading ...(mp3, 2.35 MB) Download audio
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