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Haythorne, 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.*

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic beta-cells.

Nat. Commun. 10:2474 (2019)
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Diabetes is a global health problem caused primarily by the inability of pancreatic beta-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of beta-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 beta V59M 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 beta-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 beta-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of beta-cells in diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Insulin-secretion; Gene-expression; Glucose; Islets; State; Transcriptome; Dysfunction; Mechanisms; Nadh; Mass
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 2474 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-251
DOI 10.1038/s41467-019-10189-x
WOS ID WOS:000470248100006
Scopus ID 85067065277
PubMed ID 31171772
Erfassungsdatum 2019-06-13
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