The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual as it implies that ATP flux is governed, to a significant extent, by ATP supply, while it is predominantly demand-driven in other cell types. Metabolic control is generally shared between different processes, but potential control of ATP consumption over β-cell bioenergetics has been largely ignored to date. The present paper offers a brief overview of experimental evidence that demonstrates ATP flux control by glucose-fuelled oxidative phosphorylation. Based on old and new data, it is argued that ATP supply does not hold exclusive control over ATP flux, but shares it with ATP demand, and that the distribution of control is flexible. Quantification of the bioenergetic control distribution will be important from basic and clinical perspectives, but precise measurement of the cytosolic ATP/ADP ratio is complicated by adenine nucleotide compartmentalisation. Metabolic control analysis of β-cell bioenergetics will likely clarify the mechanisms by which glucose and fatty acids amplify and potentiate GSIS, respectively. Moreover, such analysis may offer hints as to how ATP flux control shifts from ATP supply to ATP demand during the development of type 2 diabetes, and why prolonged sulfonylurea treatment causes β-cell deterioration.
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June 2018
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The structure of a Nucleosome, in which DNA is wrapped around a histone core. In this issue of Biochemical Society Transactions, Taniguchi et al. review recent advances in exploring Nucleosome-level 3D organization of the genome; for details see pages 491–501.
Review Article|
April 17 2018
Control of pancreatic β-cell bioenergetics
Charles Affourtit;
1School of Biomedical and Healthcare Sciences, University of Plymouth, The John Bull Building, Plymouth Science Park, 16 Research Way, PL6 8BU Plymouth, U.K.
Correspondence: Charles Affourtit (charles.affourtit@plymouth.ac.uk)
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Ben Alberts;
Ben Alberts
*
1School of Biomedical and Healthcare Sciences, University of Plymouth, The John Bull Building, Plymouth Science Park, 16 Research Way, PL6 8BU Plymouth, U.K.
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Jonathan Barlow;
Jonathan Barlow
†
1School of Biomedical and Healthcare Sciences, University of Plymouth, The John Bull Building, Plymouth Science Park, 16 Research Way, PL6 8BU Plymouth, U.K.
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Jane E. Carré;
Jane E. Carré
1School of Biomedical and Healthcare Sciences, University of Plymouth, The John Bull Building, Plymouth Science Park, 16 Research Way, PL6 8BU Plymouth, U.K.
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Anthony G. Wynne
Anthony G. Wynne
1School of Biomedical and Healthcare Sciences, University of Plymouth, The John Bull Building, Plymouth Science Park, 16 Research Way, PL6 8BU Plymouth, U.K.
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Publisher: Portland Press Ltd
Received:
February 02 2018
Revision Received:
March 06 2018
Accepted:
March 08 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (3): 555–564.
Article history
Received:
February 02 2018
Revision Received:
March 06 2018
Accepted:
March 08 2018
Citation
Charles Affourtit, Ben Alberts, Jonathan Barlow, Jane E. Carré, Anthony G. Wynne; Control of pancreatic β-cell bioenergetics. Biochem Soc Trans 19 June 2018; 46 (3): 555–564. doi: https://doi.org/10.1042/BST20170505
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