PUBLICATION
Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
- Authors
- Karampelias, C., Rezanejad, H., Rosko, M., Duan, L., Lu, J., Pazzagli, L., Bertolino, P., Cesta, C.E., Liu, X., Korbutt, G.S., Andersson, O.
- ID
- ZDB-PUB-210609-3
- Date
- 2021
- Source
- Nature communications 12: 3362 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Animals, Newborn
- Carbon/metabolism*
- Carnitine/metabolism
- Cell Differentiation/drug effects*
- Cell Differentiation/genetics
- Cells, Cultured
- Folate Receptor 1/genetics
- Folate Receptor 1/metabolism*
- Gene Expression Regulation/drug effects
- Humans
- Insulin-Secreting Cells/cytology
- Insulin-Secreting Cells/metabolism*
- Larva/genetics
- Larva/metabolism
- Leucovorin/pharmacology*
- Metabolic Networks and Pathways/drug effects
- Mice
- Pyrimidines/metabolism
- Swine
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 34099692 Full text @ Nat. Commun.
Citation
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. 12:3362.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping