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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)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Insulin-secretion; Gene-expression; Glucose; Islets; State; Transcriptome; Dysfunction; Mechanisms; Nadh; Mass
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 2474 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed