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Title

Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degradation in 3T3-L1 adipocytes

AuthorsGonzález-Muñoz, Elena; López-Iglesias, Carmen; Calvo, María; Palacín, Manuel; Zorzano, Antonio; Camps, Marta
Issue Date2009
PublisherEndocrine Society
CitationEndocrinology 150(8): 3493-3502 (2009)
AbstractCaveolae are a specialized type of lipid rafts that are stabilized by oligomers of caveolin protein. Caveolae are particularly enriched in adipocytes. Here we analyzed the effects of caveolin-1 knockdown and caveolae ablation on adipocyte function. To this end, we obtained several multiclonal mouse 3T3-L1 cell lines with a reduced expression of caveolin-1 (95% reduction) by a small interfering RNA approach using lentiviral vectors. Control cell lines were obtained by lentiviral infection with lentiviral vectors encoding appropriate scrambled RNAs. Caveolin-1 knockdown adipocytes showed a drastic reduction in the number of caveolae (95% decrease) and cholera toxin labeling was reorganized in dynamic plasma membrane microdomains. Caveolin-1 depletion caused a specific decrease in glucose transporter 4 (GLUT4) and insulin receptor protein levels. This reduction was not the result of a generalized defect in adipocyte differentiation or altered gene expression but was explained by faster degradation of these proteins. Caveolin-1 knockdown adipocytes showed reductions in insulin-stimulated glucose transport, insulin-triggered GLUT4 recruitment to the cell surface, and insulin receptor activation. In all, our data indicate that caveolin-1 loss of function reduces maximal insulin response through lowered stability and diminished expression of insulin receptors and GLUT4. We propose that caveolin-1/caveolae control insulin action in adipose cells. Copyright © 2009 by The Endocrine Society.
URIhttp://hdl.handle.net/10261/75555
DOI10.1210/en.2008-1520
Identifiersdoi: 10.1210/en.2008-1520
issn: 0013-7227
e-issn: 1945-7170
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