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dc.contributor.authorCarrasco-Pozo, Catalina
dc.contributor.authorTan, Kah Ni
dc.contributor.authorReyes-Farias, Marjorie
dc.contributor.authorDe La Jara, Nicole
dc.contributor.authorNgo, Shyuan Thieu
dc.contributor.authorFernando Garcia-Diaz, Diego
dc.contributor.authorLlanos, Paola
dc.contributor.authorJose Cires, Maria
dc.contributor.authorBorges, Karin
dc.date.accessioned2019-11-04T05:00:12Z
dc.date.available2019-11-04T05:00:12Z
dc.date.issued2016
dc.identifier.issn2213-2317
dc.identifier.doi10.1016/j.redox.2016.08.007
dc.identifier.urihttp://hdl.handle.net/10072/388891
dc.description.abstractStudying rats fed high cholesterol diet and a pancreatic β-cell line (Min6), we aimed to determine the mechanisms by which quercetin protects against cholesterol-induced pancreatic β-cell dysfunction and impairments in glycemic control. Quercetin prevented the increase in total plasma cholesterol, but only partially prevented the high cholesterol diet-induced alterations in lipid profile. Quercetin prevented cholesterol-induced decreases in pancreatic ATP levels and mitochondrial bioenergetic dysfunction in Min6 cells, including decreases in mitochondrial membrane potentials and coupling efficiency in the mitochondrial respiration (basal and maximal oxygen consumption rate (OCR), ATP-linked OCR and reserve capacity). Quercetin protected against cholesterol-induced apoptosis of Min6 cells by inhibiting caspase-3 and -9 activation and cytochrome c release. Quercetin prevented the cholesterol-induced decrease in antioxidant defence enzymes from pancreas (cytosolic and mitochondrial homogenates) and Min6 cells and the cholesterol-induced increase of cellular and mitochondrial oxidative status and lipid peroxidation. Quercetin counteracted the cholesterol-induced activation of the NFκB pathway in the pancreas and Min6 cells, normalizing the expression of pro-inflammatory cytokines. Quercetin inhibited the cholesterol-induced decrease in sirtuin 1 expression in the pancreas and pancreatic β-cells. Taken together, the anti-apoptotic, antioxidant and anti-inflammatory properties of quercetin, and its ability to protect and improve mitochondrial bioenergetic function are likely to contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction, thereby preserving glucose-stimulated insulin secretion (GSIS) and glycemic control. Specifically, the improvement of ATP-linked OCR and the reserve capacity are important mechanisms for protection of quercetin. In addition, the inhibition of the NFκB pathway is an important mechanism for the protection of quercetin against cytokine mediated cholesterol-induced glycemic control impairment. In summary, our data highlight cellular, molecular and bioenergetic mechanisms underlying quercetin's protective effects on β-cells in vitro and in vivo, and provide a scientifically tested foundation upon which quercetin can be developed as a nutraceutical to preserve β-cell function.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom229
dc.relation.ispartofpageto243
dc.relation.ispartofjournalRedox Biology
dc.relation.ispartofvolume9
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode3214
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsCholesterol
dc.subject.keywordsGlycemic control
dc.titleThe deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic beta-cells, glycemic control and inflammation: In vitro and in vivo studies.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCarrasco-Pozo, C; Tan, KN; Reyes-Farias, M; De La Jara, N; Ngo, ST; Fernando Garcia-Diaz, D; Llanos, P; Jose Cires, M; Borges, K, The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic beta-cells, glycemic control and inflammation: In vitro and in vivo studies., Redox Biology, 2016, 9, pp. 229-243
dcterms.dateAccepted2016-08-18
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2019-10-30T23:25:27Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorTan, Kah Ni


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