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Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells. / Haythorne, Elizabeth; Rohm, Maria; van de Bunt, Martijn; Brereton, Melissa F; Tarasov, Andrei I; Blacker, Thomas S; Sachse, Gregor; Silva Dos Santos, Mariana; Terron Exposito, Raul; Davis, Simon; Baba, Otto; Fischer, Roman; Duchen, Michael R; Rorsman, Patrik; MacRae, James I; Ashcroft, Frances M.

In: Nature Communications, Vol. 10, No. 1, 2474, 06.06.2019.

Research output: Contribution to journalArticle

Harvard

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 2019, 'Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells', Nature Communications, vol. 10, no. 1, 2474. https://doi.org/10.1038/s41467-019-10189-x

APA

Haythorne, E., Rohm, M., van de Bunt, M., Brereton, M. F., Tarasov, A. I., Blacker, T. S., ... Ashcroft, F. M. (2019). Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells. Nature Communications, 10(1), [2474]. https://doi.org/10.1038/s41467-019-10189-x

Vancouver

Author

Haythorne, Elizabeth ; Rohm, Maria ; van de Bunt, Martijn ; Brereton, Melissa F ; Tarasov, Andrei I ; Blacker, Thomas S ; Sachse, Gregor ; Silva Dos Santos, Mariana ; Terron Exposito, Raul ; Davis, Simon ; Baba, Otto ; Fischer, Roman ; Duchen, Michael R ; Rorsman, Patrik ; MacRae, James I ; Ashcroft, Frances M. / Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Bibtex

@article{3ae351fd41e44570989b90b1bd426ed5,
title = "Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells",
abstract = "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.",
author = "Elizabeth Haythorne and Maria Rohm and {van de Bunt}, Martijn and Brereton, {Melissa F} and Tarasov, {Andrei I} and Blacker, {Thomas S} and Gregor Sachse and {Silva Dos Santos}, Mariana and {Terron Exposito}, Raul and Simon Davis and Otto Baba and Roman Fischer and Duchen, {Michael R} and Patrik Rorsman and MacRae, {James I} and Ashcroft, {Frances M}",
year = "2019",
month = "6",
day = "6",
doi = "10.1038/s41467-019-10189-x",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

AU - Haythorne, Elizabeth

AU - Rohm, Maria

AU - van de Bunt, Martijn

AU - Brereton, Melissa F

AU - Tarasov, Andrei I

AU - Blacker, Thomas S

AU - Sachse, Gregor

AU - Silva Dos Santos, Mariana

AU - Terron Exposito, Raul

AU - Davis, Simon

AU - Baba, Otto

AU - Fischer, Roman

AU - Duchen, Michael R

AU - Rorsman, Patrik

AU - MacRae, James I

AU - Ashcroft, Frances M

PY - 2019/6/6

Y1 - 2019/6/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85067065277&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10189-x

DO - 10.1038/s41467-019-10189-x

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2474

ER -