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dc.contributor.authorAyer, Anita
dc.contributor.authorFazakerley, Daniel
dc.contributor.authorJames, David E
dc.contributor.authorStocker, Roland
dc.date.accessioned2021-11-17T00:30:43Z
dc.date.available2021-11-17T00:30:43Z
dc.date.issued2022-02-01
dc.identifier.issn0891-5849
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330693
dc.description.abstractInsulin resistance is one of the earliest pathological features of a suite of diseases including type 2 diabetes collectively referred to as metabolic syndrome. There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Here we review the evidence linking mitochondrial reactive oxygen species generated within mitochondria with insulin resistance in adipose tissue and skeletal muscle, two major insulin sensitive tissues. We outline the relevant mitochondria-derived reactive species, how the mitochondrial redox state is regulated, and methodologies available to measure mitochondrial reactive oxygen species. Importantly, we highlight key experimental issues to be considered when studying the role of mitochondrial reactive oxygen species in insulin resistance. Evaluating the available literature on both mitochondrial reactive oxygen species/redox state and insulin resistance in a variety of biological systems, we conclude that the weight of evidence suggests a likely role for mitochondrial reactive oxygen species in the etiology of insulin resistance in adipose tissue and skeletal muscle. However, major limitations in the methods used to study reactive oxygen species in insulin resistance as well as the lack of data linking mitochondrial reactive oxygen species and cytosolic insulin signaling pathways are significant obstacles in proving the mechanistic link between these two processes. We provide a framework to guide future studies to provide stronger mechanistic information on the link between mitochondrial reactive oxygen species and insulin resistance as understanding the source, localization, nature, and quantity of mitochondrial reactive oxygen species, their targets and downstream signaling pathways may pave the way for important new therapeutic strategies.
dc.description.sponsorshipMedical Research Council Career Development Award (MR/S007091/1)
dc.languageen
dc.publisherElsevier BV
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleThe role of mitochondrial reactive oxygen species in insulin resistance
dc.typeArticle
prism.publicationNameFree Radical Biology and Medicine
dc.identifier.doi10.17863/CAM.78138
dcterms.dateAccepted2021-11-06
rioxxterms.versionofrecord10.1016/j.freeradbiomed.2021.11.007
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11-06
dc.contributor.orcidFazakerley, Daniel [0000-0001-8241-2903]
dc.identifier.eissn1873-4596
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/S007091/1)
cam.issuedOnline2021-11-11
cam.orpheus.success2021-11-16 - Embargo set during processing via Fast-track
rioxxterms.freetoread.startdate2022-11-30


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