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dc.contributor.authorSavic, Dragana
dc.contributor.authorBall, Vicky
dc.contributor.authorCurtis, M. Kate
dc.contributor.authorSousa Fialho, Maria da Luz
dc.contributor.authorTimm, Kerstin N.
dc.contributor.authorHauton, David
dc.contributor.authorWest, James
dc.contributor.authorGriffin, Julian
dc.contributor.authorHeather, Lisa C.
dc.contributor.authorTyler, Damian J.
dc.date.accessioned2021-03-25T02:14:06Z
dc.date.available2021-03-25T02:14:06Z
dc.date.issued2021-03-23
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/319181
dc.descriptionFunder: Danish Council for Strategic Research; Grant(s): “LIFE-DNP: hyperpolarized magnetic resonance for in vivo quantification of lipid, sugar and amino acid metabolism in lifestyle related diseases”
dc.description.abstractThe diabetic heart is energetically and metabolically abnormal, with increased fatty acid oxidation and decreased glucose oxidation. One factor contributing to the metabolic dysfunction in diabetes may be abnormal handling of acetyl and acyl groups by the mitochondria. L-carnitine is responsible for their transfer across the mitochondrial membrane, therefore, supplementation with L-carnitine may provide a route to improve the metabolic state of the diabetic heart. The primary aim of this study was to use hyperpolarized magnetic resonance imaging (MRI) to investigate the effects of L-carnitine supplementation on the in vivo metabolism of [1-13C]pyruvate in diabetes. Male Wistar rats were injected with either vehicle or streptozotocin (55 mg/kg) to induce type-1 diabetes. Three weeks of daily i.p. treatment with either saline or L-carnitine (3 g/kg/day) was subsequently undertaken. In vivo cardiac function and metabolism were assessed with CINE and hyperpolarized MRI, respectively. L-carnitine supplementation prevented the progression of hyperglycemia, which was observed in untreated streptozotocin injected animals and led to reductions in plasma triglyceride and ß-hydroxybutyrate concentrations. Hyperpolarized MRI revealed that L-carnitine treatment elevated pyruvate dehydrogenase flux by 3-fold in the diabetic animals, potentially through increased buffering of excess acetyl-CoA units in the mitochondria. Improved functional recovery following ischemia was also observed in the L-carnitine treated diabetic animals.
dc.languageen
dc.publisherMDPI
dc.subjectmagnetic resonance
dc.subjectL-carnitine
dc.subjectmetabolic imaging
dc.subjectin vivo metabolism
dc.subjecthyperpolarized 13C
dc.subjectLangendorff perfusion
dc.subjectmetabolomics
dc.subjecttype-1 diabetes
dc.subjectcardiac imaging
dc.subjectstreptozotocin
dc.titleL-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI
dc.typeArticle
dc.date.updated2021-03-25T02:14:06Z
prism.issueIdentifier3
prism.publicationNameMetabolites
prism.volume11
dc.identifier.doi10.17863/CAM.66299
dcterms.dateAccepted2021-03-19
rioxxterms.versionofrecord10.3390/metabo11030191
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSavic, Dragana [0000-0002-2181-3196]
dc.contributor.orcidBall, Vicky [0000-0002-6441-0303]
dc.contributor.orcidTyler, Damian J. [0000-0002-0780-8905]
dc.identifier.eissn2218-1989
pubs.funder-project-idBritish Heart Foundation (FS/17/58/33072, RE/13/1/30181, FS/17/58/33072)
pubs.funder-project-idNovo Nordisk Foundation (Postdoctoral Fellowship)


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