title: Glimepiride activates eNOS with a mechanism Akt but not caveolin-1 dependent.
abstract: Insulin stimulates caveolin-1 and eNOS phosphorylation. The sulfonylurea glimepiride mimics several insulin actions by mechanisms that are poorly understood. Glimepiride induces caveolin-1 phosphorylation and activates PI3K and Akt in rat adipocytes. In this paper, we investigated the effect of glimepiride on eNOS activation in human endothelial cells. We found that glimepiride induces caveolin-1 and eNOS phosphorylation. To better understand the role of caveolin-1 in glimepiride action, we downregulated caveolin-1 expression by specific siRNA transfection. Caveolin-1 silencing did not change eNOS and Akt phosphorylation induced by glimepiride. On the contrary, LY294002, a specific PI3K inhibitor, blocked eNOS serine 1177 phosphorylation. These findings suggest that glimepiride induces eNOS phosphorylation in endothelial cells through an Akt-dependent mechanism, not regulated by caveolin-1.
authors.affiliation: Department of Endocrinology and Metabolism (Di.S.E.M), University of Genova, Genova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salani
authors.forename: Silvia
authors.initials: S
authors.lastname: Repetto
authors.forename: Renzo
authors.initials: R
authors.lastname: Cordera
authors.forename: Davide
authors.initials: D
authors.lastname: Maggi
mesh_terms: D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D007004:Hypoglycemic Agents; D011518:Proto-Oncogene Proteins; D013453:Sulfonylurea Compounds; C057619:glimepiride; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt