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

Christos Karampelias, Habib Rezanejad, Mandy Rosko, Likun Duan, Jing Lu, Laura Pazzagli, Philippe Bertolino, Carolyn E. Cesta, Xiaojing Liu, Gregory S. Korbutt and Olov Andersson ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23673-0

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DOI: 10.1038/s41467-021-23673-0

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