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ID 115227
著者
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
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
10
開始ページ
2474
発行日
2019-06-06
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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言語
eng
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出版社版
部局
歯学系