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DC Field | Value | Language |
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dc.contributor.author | Williamson G. | en |
dc.contributor.author | Tumova S. | en |
dc.contributor.author | Kerimi A. | en |
dc.date.accessioned | 2021-05-14T12:04:21Z | en |
dc.date.available | 2021-05-14T12:04:21Z | en |
dc.date.copyright | 2019 | en |
dc.date.created | 20190509 | en |
dc.date.issued | 2019-05-09 | en |
dc.identifier.citation | Free Radical Biology and Medicine. 137 (pp 158-168), 2019. Date of Publication: June 2019. | en |
dc.identifier.issn | 0891-5849 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/35692 | en |
dc.description.abstract | Endothelial functionality profoundly contributes to cardiovascular health. The effects of flavonoids shown to improve endothelial performance include regulating blood pressure by modulating endothelial nitric oxide synthase and NADPH oxidases, but their impact on glucose uptake and metabolism has not been explored. We treated human umbilical vein endothelial cells (HUVEC) with the flavonoid quercetin and its circulating metabolites acutely and chronically, then assessed glucose uptake, glucose metabolism, gene transcription and protein expression. Acute treatment had no effect on glucose uptake, ruling out any direct interaction with sugar transporters. Long term treatment with quercetin, but not quercetin 3-O-glucuronide or 3'-O-sulfate, significantly increased glucose uptake. Heme oxygenase-1 (HO-1) was induced by quercetin but not its conjugates, but was not implicated in the glucose uptake stimulation since hemin, a classical inducer of HO-1, did not affect glucose metabolism. Quercetin increased stability of the transcription factor hypoxia induced factor 1alpha (HIF1alpha), a powerful stimulant of glucose metabolism, which was also paralleled by treatment with a prolyl-4-hydroxylase inhibitor dimethyloxalylglycine (DMOG). 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which regulates the rate of glycolysis, was upregulated by both quercetin and DMOG. Pyruvate dehydrogenase kinase (PDK) isoforms regulate pyruvate dehydrogenase; PDK2 and PDK4 were down-regulated by both effectors, but only DMOG also upregulated PDK1 and PDK3. Quercetin, but not DMOG, increased glucose-6-phosphate dehydrogenase. Chronic quercetin treatment also stimulated glucose transport across the HUVEC monolyer in a 3D culture model. Gene expression of several flavonoid transporters was repressed by quercetin, but this was either abolished (Organic anion transporter polypeptide 4C1) or reversed (Multidrug resistance gene 1) by both conjugates. We conclude that quercetin and its circulating metabolites differentially modulate glucose uptake/metabolism in endothelial cells, through effects on HIF1alpha and transcriptional regulation of energy metabolism.Copyright © 2019 | en |
dc.language | en | en |
dc.language | English | en |
dc.publisher | Elsevier Inc. (E-mail: usjcs@elsevier.com) | en |
dc.relation.ispartof | Free Radical Biology and Medicine | en |
dc.title | Long term treatment with quercetin in contrast to the sulfate and glucuronide conjugates affects HIF1alpha stability and Nrf2 signaling in endothelial cells and leads to changes in glucose metabolism. | en |
dc.type | Article | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.023 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 31029788 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31029788] | en |
dc.identifier.source | 2001920007 | en |
dc.identifier.institution | (Tumova, Kerimi, Williamson) School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, United Kingdom (Williamson) Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Notting Hill BASE Facility, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia | en |
dc.description.address | G. Williamson, Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Notting Hill BASE facility, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia. E-mail: gary.williamson1@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2019 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Williamson G.; gary.williamson1@monash.edu | en |
item.fulltext | No Fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
Appears in Collections: | Articles |
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