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

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.

Publication Information

Karampelias, C., Rezanejad, H., Rosko, M., Duan, L., Lu, J., Pazzagli, L., Bertolino, P., Cesta, C. E., Liu, X., Korbutt, G. S., & Andersson, O. (2021). Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation. Nature Communications, 12(1), 3362–13. https://doi.org/10.1038/s41467-021-23673-0