title: Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes.
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 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.
authors.affiliation: Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA; Koch Institute at MIT, 500 Main Street, Cambridge, MA 02139, USA.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, University of Southern California, Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Villani
authors.affiliation: Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA; IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Buono
authors.affiliation: Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Koch Institute at MIT, 500 Main Street, Cambridge, MA 02139, USA.
authors.forename: Omer H
authors.initials: OH
authors.lastname: Yilmaz
authors.affiliation: Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Diabetes Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sneddon
authors.affiliation: GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, University of Southern California, Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Perin
authors.affiliation: Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA; IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy. Electronic address: vlongo@usc.edu.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy*; D004032:Diet; D005215:Fasting; D005951:Glucose Tolerance Test; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse