Insulin and IGF-I phosphorylate eNOS in HUVECs by a caveolin-1 dependent mechanism.
Caveolae are plasmamembrane regions which take part in the regulation of intracellular trafficking and signaling of tyrosine kinase receptors. Insulin and IGF-I receptors and their intracellular substrates localize in caveolae. Also eNOS is targeted to caveolae and caveolin-1, the major caveolar protein, acts as a regulator of eNOS activity. Since Insulin and IGF-I phosphorylate and activate eNOS, we investigated the role of caveolin-1 in Insulin and IGF-I stimulated eNOS activity. Here we show that: (1) in human endothelial cells, Insulin and IGF-I stimulate eNOS phosphorylation in a different manner both qualitatively and quantitatively; (2) caveolin-1 down regulation abolishes Insulin and IGF-I stimulated eNOS phosphorylation. These results suggest that caveolae could represent an intracellular site that contributes to differentiate IR and IGF-IR activity, and demonstrate the role of caveolin-1 in the eNOS activation by Insulin and IGF-I.
Repetto
Silvia
S
Department of Endocrinology and Metabolism, University of Genova, Genova, Italy.
Salani
Barbara
B
Maggi
Davide
D
Cordera
Renzo
R
D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D051242:Caveolin 1; D004338:Drug Combinations; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D052250:Nitric Oxide Synthase Type III