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dc.contributor.authorHaythorne, Elizabeth
dc.contributor.authorRohm, Maria
dc.contributor.authorvan de Bunt, Martijn
dc.contributor.authorBrereton, Melissa F
dc.contributor.authorTarasov, Andrei I
dc.contributor.authorBlacker, Thomas S
dc.contributor.authorSachse, Gregor
dc.contributor.authorSilva Dos Santos, Mariana
dc.contributor.authorTerron Exposito, Raul
dc.contributor.authorDavis, Simon
dc.contributor.authorBaba, Otto
dc.contributor.authorFischer, Roman
dc.contributor.authorDuchen, Michael R
dc.contributor.authorRorsman, Patrik
dc.contributor.authorMacRae, James I
dc.contributor.authorAshcroft, Frances M
dc.date.accessioned2019-08-20T12:38:45Z
dc.date.available2019-08-20T12:38:45Z
dc.date.issued2019-06-06
dc.identifier.citationHaythorne , E , Rohm , M , van de Bunt , M , Brereton , M F , Tarasov , A I , Blacker , T S , Sachse , G , Silva Dos Santos , M , Terron Exposito , R , Davis , S , Baba , O , Fischer , R , Duchen , M R , Rorsman , P , MacRae , J I & Ashcroft , F M 2019 , ' Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells ' , Nature Communications , vol. 10 , no. 1 , 2474 . https://doi.org/10.1038/s41467-019-10189-x
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 16946332
dc.identifier.otherPURE UUID: 3ae351fd-41e4-4570-989b-90b1bd426ed5
dc.identifier.otherPubMed: 31171772
dc.identifier.otherScopus: 85067065277
dc.identifier.otherORCID: /0000-0002-8883-176X/work/62751462
dc.identifier.urihttp://hdl.handle.net/2299/21609
dc.description.abstractDiabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.en
dc.format.extent17
dc.language.isoeng
dc.relation.ispartofNature Communications
dc.subjectChemistry(all)
dc.subjectBiochemistry, Genetics and Molecular Biology(all)
dc.subjectPhysics and Astronomy(all)
dc.titleDiabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cellsen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85067065277&partnerID=8YFLogxK
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1038/s41467-019-10189-x
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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