title: Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors.
abstract: Increased plasma levels of free fatty acids, including palmitic acid (PA), cause insulin resistance in endothelium characterized by a decreased synthesis of insulin-mediated vasodilator nitric oxide (NO), and by an increased production of the vasoconstrictor protein, endothelin-1. Several in vitro and in vivo studies suggest that anthocyanins, natural phenols commonly present in food and vegetables from Mediterranean Diet, exert significant cardiovascular health-promoting activities. These effects are possibly mediated by a positive regulation of the transcription factor Nrf2 and activation of cellular antioxidant and cytoprotective genes. The present study examined, at a molecular level, the effects of cyanidin-3-O-glucoside (C3G), a widely distributed anthocyanin, on PA-induced endothelial dysfunction and insulin resistance in human umbilical vein endothelial cells (HUVECs). Our results indicate that C3G pretreatment effectively reverses the effects of PA on PI3K/Akt axis, and restores eNOS expression and NO release, altered by PA. We observed that these effects were exerted by changes on the phosphorylation of IRS-1 on specific serine and tyrosine residues modulated by PA through the modulation of JNK and IKK activity. Furthermore, silencing Nrf2 transcripts demonstrated that the protective effects of C3G are directly related to the activation of Nrf2.
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Fratantonio
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy. Electronic address: fcimino@unime.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cimino
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Molonia
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ferrari
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Saija
authors.affiliation: Council for Agricultural Research and Economics, Food and Nutrition Research Centre, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Virgili
authors.affiliation: Dep. of Chemical, Biological, Pharmaceutical and Environmental Sciences, 98168, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Speciale
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D005960:Glucosides; D055504:Insulin Receptor Substrate Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D014443:Tyrosine; C526292:IRS1 protein, human; C462279:cyanidin-3-O-beta-glucopyranoside
keywords: Cyanidin-3-O-glucoside; Endothelial dysfunction; Insulin resistance; Nitric oxide; Palmitic acid