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

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.
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https://hal-univ-lyon1.archives-ouvertes.fr/hal-03666669
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Submitted on : Thursday, May 12, 2022 - 4:34:55 PM
Last modification on : Thursday, September 1, 2022 - 10:19:46 AM

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Christos Karampelias, Habib Rezanejad, Mandy Rosko, Likun Duan, Jing Lu, et al.. Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation. Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.3362. ⟨10.1038/s41467-021-23673-0⟩. ⟨hal-03666669⟩

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