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dc.contributor.authorBarzowska, Agata
dc.contributor.authorPucelik, Barbara
dc.contributor.authorPustelny, Katarzyna
dc.contributor.authorMatsuda, Alex
dc.contributor.authorMartyniak, Alicja
dc.contributor.authorStępniewski, Jacek
dc.contributor.authorMaksymiuk, Anna
dc.contributor.authorDawidowski, Maciej
dc.contributor.authorRothweiler, Ulli
dc.contributor.authorDulak, Józef
dc.contributor.authorDubin, Grzegorz
dc.contributor.authorCzarna, Anna
dc.date.accessioned2022-01-07T13:54:58Z
dc.date.available2022-01-07T13:54:58Z
dc.date.issued2021-08-31
dc.description.abstractThe rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes β-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSCderived β-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing β-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small–molecule–induced human β-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment.en_US
dc.identifier.citationBarzowska, Pucelik, Pustelny, Matsuda, Martyniak, Stępniewski, Maksymiuk, Dawidowski, Rothweiler, Dulak, Dubin, Czarna. DYRK1A kinase inhibitors promote β-cell survival and insulin homeostasis. Cells. 2021;10(9)en_US
dc.identifier.cristinIDFRIDAID 1943960
dc.identifier.doi10.3390/cells10092263
dc.identifier.issn2073-4409
dc.identifier.urihttps://hdl.handle.net/10037/23632
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.journalCells
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Endocrinology: 774en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Endokrinologi: 774en_US
dc.titleDYRK1A kinase inhibitors promote β-cell survival and insulin homeostasisen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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