Details

Autor(en) / Beteiligte

• González-Muñoz, Elena
• López-Iglesias, Carmen
• Calvo, Maria
• Palacín, Manuel
• Zorzano, Antonio
• Camps, Marta

Titel

Caveolin-1 Loss of Function Accelerates Glucose Transporter 4 and Insulin Receptor Degradation in 3T3-L1 Adipocytes

Ist Teil von

• Endocrinology (Philadelphia), 2009-08, Vol.150 (8), p.3493-3502

Ort / Verlag

Chevy Chase, MD: Endocrine Society

Erscheinungsjahr

2009

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Caveolae 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. Caveolin-1 deficiency in adipocytes has a direct effect on the expression of IR and GLUT4 proteins, independently of insulin levels, demonstrating a main role of caveolin-1 in controlling expression of proteins crucial in states of insulin resistance and obesity.