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dc.contributor.authorHewawasam, NVen
dc.contributor.authorLhaf, Fen
dc.contributor.authorTaylor, HAen
dc.contributor.authorViloria, Ken
dc.contributor.authorAustin, Aen
dc.contributor.authorKing, Aen
dc.contributor.authorJones, Pen
dc.contributor.authorJones, Len
dc.contributor.authorTurner, MDen
dc.contributor.authorHill, NJen
dc.date.accessioned2021-08-13T10:18:48Z
dc.date.issued2020-09-25en
dc.identifier.issn2045-2322en
dc.identifier.other15741en
dc.identifier.urihttp://hdl.handle.net/10026.1/17577
dc.description.abstract

<jats:title>Abstract</jats:title> <jats:p>Regenerative medicine approaches to enhancing beta cell growth and survival represent potential treatments for diabetes. It is known that growth factors such as insulin, IGF-1 and HGF support beta cell growth and survival, but in people with type 2 diabetes the destructive effects of metabolic stress predominate and beta cell death or dysfunction occurs. In this study we explore the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signalling is dependent on the presence of cell surface receptors. Endosomal trafficking and subsequent recycling or degradation of these receptors is controlled by the Rab GTPase family of proteins. We show that Rab7a siRNA inhibition enhances IGF-1 and HGF signalling in beta cells and increases expression of the growth factor receptors IGF-1R and c-Met. Furthermore, Rab7a inhibition promotes beta cell growth and islet survival, and protects against activation of apoptosis and autophagy pathways under conditions of metabolic stress. This study therefore demonstrates that Rab7a-mediated trafficking of growth factor receptors controls beta cell survival. Pharmaceutical Rab7a inhibition may provide a means to promote beta cell survival in the context of metabolic stress and prevent the onset of type 2 diabetes.</jats:p>

en
dc.languageenen
dc.language.isoenen
dc.publisherNature Research (part of Springer Nature)en
dc.titleModulation of Rab7a-mediated growth factor receptor trafficking inhibits islet beta cell apoptosis and autophagy under conditions of metabolic stressen
dc.typeJournal Article
plymouth.issue1en
plymouth.volume10en
plymouth.journalScientific Reportsen
dc.identifier.doi10.1038/s41598-020-72939-yen
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dcterms.dateAccepted2020-09-09en
dc.rights.embargodate2021-08-14en
dc.identifier.eissn2045-2322en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1038/s41598-020-72939-yen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-09-25en
rioxxterms.typeJournal Article/Reviewen


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