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PXD012979

PXD012979 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDiabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells
DescriptionDiabetes 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.
HostingRepositoryPRIDE
AnnounceDate2019-04-10
AnnouncementXMLSubmission_2019-06-20_03:35:52.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD012979
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRoman Fischer
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListOxidation; Oxidation
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-05 07:29:03ID requested
12019-04-10 12:36:26announced
22019-06-20 03:35:54announcedUpdated publication reference for PubMed record(s): 31171772.
Publication List
Haythorne E, Rohm M, van de Bunt M, Brereton MF, Tarasov AI, Blacker TS, Sachse G, Silva Dos Santos M, Terron Exposito R, Davis S, Baba O, Fischer R, Duchen MR, Rorsman P, MacRae JI, Ashcroft FM, -cells. Nat Commun, 10(1):2474(2019) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: diabetes, β-cells, islets, pancreas
Contact List
Roman Fischer
contact affiliationDiscovery Proteomics Facility University of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliationUniversity of Oxford
contact emailroman.fischer@ndm.ox.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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Repository Record List
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