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Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation

Author

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  • Christos Karampelias

    (Karolinska Institutet)

  • Habib Rezanejad

    (Department of Surgery and Alberta Diabetes Institute, University of Alberta)

  • Mandy Rosko

    (Department of Surgery and Alberta Diabetes Institute, University of Alberta)

  • Likun Duan

    (NC State University)

  • Jing Lu

    (Karolinska Institutet)

  • Laura Pazzagli

    (Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet)

  • Philippe Bertolino

    (Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Claude Bernard University)

  • Carolyn E. Cesta

    (Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet)

  • Xiaojing Liu

    (NC State University)

  • Gregory S. Korbutt

    (Department of Surgery and Alberta Diabetes Institute, University of Alberta)

  • Olov Andersson

    (Karolinska Institutet)

Abstract

Diabetes can be caused by an insufficiency in β-cell mass. Here, we performed a genetic screen in a zebrafish model of β-cell loss to identify pathways promoting β-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated β-cell differentiation in zebrafish. Treatment with folinic acid also stimulated β-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 β-cell differentiation originated from ductal cells. Mechanistically, comparative metabolomic analysis of zebrafish with/without β-cell ablation and with/without folinic acid treatment indicated β-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 β-cells.

Suggested Citation

  • Christos Karampelias & Habib Rezanejad & Mandy Rosko & Likun Duan & Jing Lu & Laura Pazzagli & Philippe Bertolino & Carolyn E. Cesta & Xiaojing Liu & Gregory S. Korbutt & Olov Andersson, 2021. "Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23673-0
    DOI: 10.1038/s41467-021-23673-0
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