Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes

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dc.contributor.authorDooley, James
dc.contributor.authorTian, Lei
dc.contributor.authorSchonefeldt, Susann
dc.contributor.authorDelghingaro-Augusto, Viviane
dc.contributor.authorGarcia-Perez, Josselyn E
dc.contributor.authorPasciuto, Emanuela
dc.contributor.authorDi Marino, Daniele
dc.contributor.authorCarr, Edward J
dc.contributor.authorOskolkov, Nikolay
dc.contributor.authorLyssenko, Valeriya
dc.contributor.authorFranckaert, Dean
dc.contributor.authorDahlstrom, Jane
dc.contributor.authorPetrovsky, Nikolai
dc.contributor.authorSocha, L
dc.contributor.authorLinterman, Michelle A.
dc.contributor.authorGoodnow, Chris
dc.contributor.authorNolan, Christopher
dc.contributor.authorListon, Adrian
dc.date.accessioned2024-10-29T00:35:33Z
dc.date.available2024-10-29T00:35:33Z
dc.date.issued2016
dc.date.updated2024-02-04T07:15:58Z
dc.description.abstractType 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes.
dc.description.sponsorshipThis work was supported by the VIB, European Research Council (ERC) and a Juvenile Diabetes Research Foundation (JDRF) Career Development Award (A.L.) and . N.O. and V. Lyssenko acknowledge support by a Strategic Research Grant from the Swedish Research Council (2009-1039).
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn1061-4036
dc.identifier.urihttps://hdl.handle.net/1885/733722206
dc.language.isoen_AUen_AU
dc.provenancehttps://v2.sherpa.ac.uk/id/publication/1650/..."published version can be archived in institutional repository" from SHERPA/RoMEO site as at 29/10/2024
dc.publisherNature Publishing Group
dc.relationhttp://purl.org/au-research/grants/nhmrc/1028108
dc.rights© 2016 The authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceNature Genetics
dc.titleGenetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes
dc.typeJournal article
dcterms.accessRightsOpen Access
local.bibliographicCitation.issue5
local.bibliographicCitation.lastpage527
local.bibliographicCitation.startpage519
local.contributor.affiliationDooley, James, VIB
local.contributor.affiliationTian, Lei, University of Leuven
local.contributor.affiliationSchonefeldt, Susann, Center for the Biology of Disease
local.contributor.affiliationDelghingaro-Augusto, Viviane, College of Health and Medicine, ANU
local.contributor.affiliationGarcia-Perez, Josselyn E, Center for the Biology of Disease
local.contributor.affiliationPasciuto, Emanuela, Center for the Biology of Disease
local.contributor.affiliationDi Marino, Daniele, Università della Svizzera Italiana
local.contributor.affiliationCarr, Edward J, Babraham Institute
local.contributor.affiliationOskolkov, Nikolay, Lund University
local.contributor.affiliationLyssenko, Valeriya, Lund University
local.contributor.affiliationFranckaert, Dean , VIB
local.contributor.affiliationDahlstrom, Jane, College of Health and Medicine, ANU
local.contributor.affiliationPetrovsky, Nikolai, Flinders Medical Centre
local.contributor.affiliationSocha, L, College of Health and Medicine, ANU
local.contributor.affiliationLinterman, Michelle A., Cambridge Institute for Medical Research
local.contributor.affiliationGoodnow, Chris, Garvan Insitutute
local.contributor.affiliationNolan, Christopher, College of Health and Medicine, ANU
local.contributor.affiliationListon, Adrian , University of Leuven
local.contributor.authoremailu3725583@anu.edu.au
local.contributor.authoruidDelghingaro-Augusto, Viviane, u4732956
local.contributor.authoruidDahlstrom, Jane, u3725583
local.contributor.authoruidSocha, L, u3266083
local.contributor.authoruidNolan, Christopher, u1820721
local.description.notesImported from ARIES
local.identifier.absfor320208 - Endocrinology
local.identifier.ariespublicationu4844039xPUB44
local.identifier.citationvolume48
local.identifier.doi10.1038/ng.3531
local.identifier.scopusID2-s2.0-84961391380
local.identifier.thomsonIDWOS:000374834100011
local.identifier.uidSubmittedByu4844039
local.publisher.urlhttps://www.nature.com/
local.type.statusPublished Version
publicationvolume.volumeNumber48

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