Expression of Caveolin 1 Is Enhanced by DNA Demethylation during Adipocyte Differentiation. Status of Insulin Signaling
Autor: | Carlos de Miguel, Sara Palacios-Ortega, José Alfredo Martínez, Fermín I. Milagro, Maider Varela-Guruceaga |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Leptin
Physiology medicine.medical_treatment Cellular differentiation Caveolin 1 lcsh:Medicine Biochemistry Mice Cell Signaling Insulin Signaling Cascade Cell differentiation Adipocytes Insulin lcsh:Science Promoter Regions Genetic Regulation of gene expression DNA methylation Multidisciplinary Adipogenesis Cell Differentiation Exons Signaling Cascades Physiological Parameters cardiovascular system Carbohydrate Metabolism Epigenetics Adiponectin Signal transduction DNA modification Research Article Signal Transduction medicine.medical_specialty Cell Survival Biology Deoxyglucose Glucose Signaling Internal medicine 3T3-L1 Cells medicine Genetics Animals Obesity Biology and life sciences Interleukin-6 lcsh:R Body Weight Biological Transport Cell Biology DNA DNA Methylation Hormones Introns Insulin receptor Glucose Endocrinology DNA demethylation Metabolism Gene Expression Regulation biology.protein lcsh:Q CpG Islands Insulin-Dependent Signal Transduction |
Zdroj: | PLoS ONE Dadun. Depósito Académico Digital de la Universidad de Navarra instname PLoS ONE, Vol 9, Iss 4, p e95100 (2014) |
ISSN: | 1932-6203 |
Popis: | Caveolin 1 (Cav-1) is an essential constituent of adipocyte caveolae which binds the beta subunit of the insulin receptor (IR) and is implicated in the regulation of insulin signaling. We have found that, during adipocyte differentiation of 3T3-L1 cells the promoter, exon 1 and first intron of the Cav-1 gene undergo a demethylation process that is accompanied by a strong induction of Cav-1 expression, indicating that epigenetic mechanisms must have a pivotal role in this differentiation process. Furthermore, IR, PKB-Akt and Glut-4 expression are also increased during the differentiation process suggesting a coordinated regulation with Cav-1. Activation of Cav-1 protein by phosphorylation arises during the differentiation process, yet in fully mature adipocytes insulin is no longer able to significantly increase Cav-1 phosphorylation. However, these long-term differentiated cells are still able to respond adequately to insulin, increasing IR and PKB-Akt phosphorylation and glucose uptake. The activation of Cav-1 during the adipocyte differentiation process could facilitate the maintenance of insulin sensitivity by these fully mature adipocytes isolated from additional external stimuli. However, under the influence of physiological conditions associated to obesity, such as chronic inflammation and hypoxia, insulin sensitivity would finally be compromised. |
Databáze: | OpenAIRE |
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