Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure
dc.contributor.author | Son, J. | |
dc.contributor.author | Du, W. | |
dc.contributor.author | Esposito, M. | |
dc.contributor.author | Shariati, K. | |
dc.contributor.author | Ding, H. | |
dc.contributor.author | Kang, Y. | |
dc.contributor.author | Accili, D. | |
dc.date.accessioned | 2024-08-12T19:29:39Z | |
dc.date.available | 2024-08-12T19:29:39Z | |
dc.date.issued | 2023-02-02 | |
dc.identifier.citation | Son, J., Du, W., Esposito, M. et al. Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure. Nat Commun 14, 558 (2023). https://doi.org/10.1038/s41467-023-36315-4 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.pmid | 36732513 | |
dc.identifier.doi | 10.1038/s41467-023-36315-4 | |
dc.identifier.uri | http://hdl.handle.net/10150/674193 | |
dc.description.abstract | Type 2 diabetes (T2D) is associated with β-cell dedifferentiation. Aldehyde dehydrogenase 1 isoform A3 (ALHD1A3) is a marker of β-cell dedifferentiation and correlates with T2D progression. However, it is unknown whether ALDH1A3 activity contributes to β-cell failure, and whether the decrease of ALDH1A3-positive β-cells (A+) following pair-feeding of diabetic animals is due to β-cell restoration. To tackle these questions, we (i) investigated the fate of A+ cells during pair-feeding by lineage-tracing, (ii) somatically ablated ALDH1A3 in diabetic β-cells, and (iii) used a novel selective ALDH1A3 inhibitor to treat diabetes. Lineage tracing and functional characterization show that A+ cells can be reconverted to functional, mature β-cells. Genetic or pharmacological inhibition of ALDH1A3 in diabetic mice lowers glycemia and increases insulin secretion. Characterization of β-cells following ALDH1A3 inhibition shows reactivation of differentiation as well as regeneration pathways. We conclude that ALDH1A3 inhibition offers a therapeutic strategy against β-cell dysfunction in diabetes. © 2023, The Author(s). | |
dc.language.iso | en | |
dc.publisher | Nature Research | |
dc.rights | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License. | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure | |
dc.type | Article | |
dc.type | text | |
dc.contributor.department | Department of Pharmacy Practice & Science, College of Pharmacy, University of Arizona | |
dc.identifier.journal | Nature Communications | |
dc.description.note | Open access journal | |
dc.description.collectioninformation | This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu. | |
dc.eprint.version | Final Published Version | |
dc.source.journaltitle | Nature Communications | |
refterms.dateFOA | 2024-08-12T19:29:39Z |