Highlights

• •Fasting mimicking diet induces prenatal-development gene expression in adult pancreas
• •FMD promotes Ngn3 expression to generate insulin-producing β cells
• •Cycles of FMD reverse β-cell failure and rescue mice from T1D and T2D
• •Inhibition of PKA or mTOR promotes Ngn3-driven β-cell regeneration in human T1D islets

Summary

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.

http://www.cell.com/cell/fulltext/S0092-8674(17)30130-7