title: Effects of high glucose on caveolin-1 and insulin signaling in 3T3-L1 adipocytes.
abstract: Adipocytes exposed to high glucose concentrations exhibit impaired metabolic function, including an increase of oxidative and proinflammatory factors that might favor the development of insulin resistance. Caveolin-1 (Cav-1) is a key mediator of the insulin transduction pathway whose expression is significantly enhanced during adipocyte differentiation. In this work, we studied the effects of high glucose concentration on the regulation of Cav-1 expression and activation and its relation to the insulin signaling pathway during the adipogenic process and in long-term differentiated adipocytes. Both, long-term high glucose exposure during adipogenesis and short-term glucose incubation of mature adipocytes, promoted triglyceride accumulation in 3T3-L1 cells. The short-term exposure of mature adipocytes to high glucose significantly reduced the sensitivity to insulin of Cav-1, insulin receptor (IR) and potein kinase B (AKT-2) phosphorylation, as well as insulin-induced deoxyglucose uptake. Adipocytes differentiated in the presence of high glucose lost Cav-1 and IR response to insulin-stimulated phosphorylation, but maintained the insulin sensitivity of AKT-2 phosphorylation and deoxyglucose uptake. Although long-term high glucose exposure increased DNA methylation in Cav-1 promoter, Cav-1 expression was not affected. Moreover, these cells showed an increase of Cav-1, IR and AKT-2 protein content, pointing to an adaptive response induced by the long-term high glucose exposure.
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain; Centre for Nutrition Research. University of Navarra, Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Palacios-Ortega
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain; Centre for Nutrition Research. University of Navarra, Pamplona, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Varela-Guruceaga
authors.affiliation: Centre for Nutrition Research. University of Navarra, Pamplona, Spain; Department of Nutrition, Food Sciences and Physiology. University of Navarra, Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain; Centre for Nutrition Research. University of Navarra, Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de Miguel
authors.affiliation: Centre for Nutrition Research. University of Navarra, Pamplona, Spain; Department of Nutrition, Food Sciences and Physiology. University of Navarra, Pamplona, Spain; CIBERobn, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Fermín I
authors.initials: FI
authors.lastname: Milagro
keywords: 3T3-L1; DNA methylation; GLUT4; adipogenesis; glucose uptake; insulin receptor; leptin