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Reinforcing one-carbon metabolism via folic acid/Folr1 promotes ß-cell differentiation.
Karampelias, Christos; Rezanejad, Habib; Rosko, Mandy; Duan, Likun; Lu, Jing; Pazzagli, Laura; Bertolino, Philippe; Cesta, Carolyn E; Liu, Xiaojing; Korbutt, Gregory S; Andersson, Olov.
Afiliação
  • Karampelias C; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
  • Rezanejad H; Department of Surgery and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Rosko M; Department of Surgery and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Duan L; Department of Molecular and Structural Biochemistry, NC State University, Raleigh, NC, USA.
  • Lu J; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
  • Pazzagli L; Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Bertolino P; Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Claude Bernard University, Lyon, France.
  • Cesta CE; Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • Liu X; Department of Molecular and Structural Biochemistry, NC State University, Raleigh, NC, USA.
  • Korbutt GS; Department of Surgery and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Andersson O; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. olov.andersson@ki.se.
Nat Commun ; 12(1): 3362, 2021 06 07.
Article em En | MEDLINE | ID: mdl-34099692
Diabetes can be caused by an insufficiency in ß-cell mass. Here, we performed a genetic screen in a zebrafish model of ß-cell loss to identify pathways promoting ß-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated ß-cell differentiation in zebrafish. Treatment with folinic acid also stimulated ß-cell differentiation in cultures of neonatal pig islets, showing that the effect could be translated to a mammalian system. In both zebrafish and neonatal pig islets, the increased ß-cell differentiation originated from ductal cells. Mechanistically, comparative metabolomic analysis of zebrafish with/without ß-cell ablation and with/without folinic acid treatment indicated ß-cell regeneration could be attributed to changes in the pyrimidine, carnitine, and serine pathways. Overall, our results suggest evolutionarily conserved and previously unknown roles for folic acid and one-carbon metabolism in the generation of ß-cells.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Carbono / Diferenciação Celular / Leucovorina / Células Secretoras de Insulina / Receptor 1 de Folato Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Carbono / Diferenciação Celular / Leucovorina / Células Secretoras de Insulina / Receptor 1 de Folato Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article