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dc.contributor.authorAffourtit, Cen
dc.contributor.authorAlberts, Ben
dc.contributor.authorBarlow, Jen
dc.contributor.authorCarré, JEen
dc.contributor.authorWynne, AGen

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.

dc.publisherPortland Pressen
dc.subjectinsulin secretionen
dc.subjectmetabolic control analysisen
dc.subjectmitochondrial respirationen
dc.subjectoxidative phosphorylationen
dc.subjectpancreatic β-cellen
dc.titleControl of pancreatic β-cell bioenergetics.en
dc.typeJournal Article
plymouth.journalBiochemical Society Transactionsen
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
dc.rights.embargoperiodNot knownen
rioxxterms.typeJournal Article/Reviewen
plymouth.funderWhy do pancreatic beta cells waste energy?::MRCen

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