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dc.contributor.authorArya, Swati
dc.contributor.authorGourley, Adam J.
dc.contributor.authorPenedo , J. Carlos
dc.contributor.authorBlindauer, Claudia A.
dc.contributor.authorStewart, Alan J.
dc.identifier.citationArya , S , Gourley , A J , Penedo , J C , Blindauer , C A & Stewart , A J 2021 , ' Fatty acids may influence insulin dynamics through modulation of albumin-Zn 2+ interactions ' , BioEssays , vol. 43 , no. 12 , 202100172 .
dc.identifier.otherPURE: 276265438
dc.identifier.otherPURE UUID: 17de77da-9da9-4f30-b041-cd7752028315
dc.identifier.otherORCID: /0000-0002-5807-5385/work/102725107
dc.identifier.otherORCID: /0000-0003-4580-1840/work/102725464
dc.identifier.otherORCID: /0000-0001-7978-9507/work/102725796
dc.identifier.otherScopus: 85118368278
dc.descriptionWe thank the Leverhulme Trust (grant no. RPG-2017-214), the Scottish Funding Council (through a St Andrews Restarting Research Fund award) and the Wellcome Trust (through an Institutional Strategic Support Fund award; grant no. 204821/Z/16/Z) for funding.en
dc.description.abstractInsulin is stored within the pancreas in an inactive Zn2+-bound hexameric form prior to release. Similarly, clinical insulins contain Zn2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn2+. The Zn2+-binding properties of HSA are attenuated by non-esterified fatty acids (NEFAs) also transported by HSA. Elevated NEFA concentrations are associated with obesity and type 2 diabetes. Here we present the hypothesis that higher NEFA levels in obese and/or diabetic individuals may contribute to insulin resistance and affect therapeutic insulin dose-response profiles, through modulation of HSA/Zn2+ dynamics. We envisage this novel concept to have important implications for personalised treatments and management of diabetes-related conditions in the future.
dc.rightsCopyright © 2021 The Authors. BioEssays published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectFörster resonance energy transferen
dc.subjectInsulin decomplexationen
dc.subjectInsulin resistanceen
dc.subjectNon-esterified fatty acidsen
dc.subjectSerum albuminen
dc.subjectQH301 Biologyen
dc.subjectRM Therapeutics. Pharmacologyen
dc.titleFatty acids may influence insulin dynamics through modulation of albumin-Zn2+ interactionsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.School of Physics and Astronomyen
dc.description.statusPeer revieweden

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