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dc.contributor.authorCarrasco-Pozo, Catalina
dc.contributor.authorGotteland, Martin
dc.contributor.authorCastillo, Rodrigo L
dc.contributor.authorChen, Chen
dc.description.abstractCholesterol plays an important role in inducing pancreatic β-cell dysfunction, characterized by an impaired insulin secretory response to glucose, representing a hallmark of the transition from pre-diabetes to diabetes. 3,4 dihydroxyphenylacetic acid (ES) is a scarcely studied microbiota-derived metabolite of quercetin with antioxidant properties. The aim of this study was to determine the protective effect of ES against apoptosis, mitochondrial dysfunction and oxidative stress induced by cholesterol in Min6 pancreatic β-cells. Cholesterol decreased viability, induced apoptosis and mitochondrial dysfunction by reducing complex I activity, mitochondrial membrane potential, ATP levels and oxygen consumption. Cholesterol promoted oxidative stress by increasing cellular and mitochondrial reactive oxygen species and lipid peroxidation and decreasing antioxidant enzyme activities; in addition, it slightly increased Nrf2 translocation to the nucleus. These events resulted in the impairment of the glucose-induced insulin secretion. ES increased Nrf2 translocation to the nucleus and protected pancreatic β-cells against impaired insulin secretion induced by cholesterol by preventing oxidative stress, apoptosis and mitochondrial dysfunction. Nrf2 activation seems to be involved in the mechanisms underlying the antioxidant protection exerted by ES in addition to preventing the disruption of antioxidant enzymatic defenses. Although additional in vivo experiments are required, this metabolite is suggested as a promising drug target for the prevention of the pathological development from a pre-diabetic to a diabetic state.
dc.relation.ispartofjournalExperimental Cell Research
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchClinical Sciences
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsCell Biology
dc.subject.keywords3,4 dihydroxyphenylacetic acid
dc.title3,4-dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, protects against pancreatic beta-cells dysfunction induced by high cholesterol
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCarrasco-Pozo, C; Gotteland, M; Castillo, RL; Chen, C, 3,4-dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, protects against pancreatic beta-cells dysfunction induced by high cholesterol, Experimental Cell Research, 2015, 334 (2), pp. 270-282
gro.hasfulltextNo Full Text
gro.griffith.authorChen, Chen
gro.griffith.authorCarrasco Pozo, Catalina A.

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