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ID 115227
Haythorne, Elizabeth University of Oxford
Rohm, Maria University of Oxford|Helmholtz Center Munich
van de Bunt, Martijn University of Oxford|Novo Nordisk A/S
Brereton, Melissa F. University of Oxford
Tarasov, Andrei I. University of Oxford
Blacker, Thomas S. University College London
Sachse, Gregor University of Oxford
Silva dos Santos, Mariana The Francis Crick Institute
Terron Exposito, Raul University of Oxford
Davis, Simon University of Oxford
Fischer, Roman University of Oxford
Duchen, Michael R. University College London
Rorsman, Patrik University of Oxford|University of Göteborg
MacRae, James I. The Francis Crick Institute
Ashcroft, Frances M. University of Oxford|University of Göteborg
Content Type
Journal Article
Diabetes 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.
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Nature Communications
Springer Nature
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Oral Sciences