Insulin and IGF-I phosphorylate eNOS in HUVECs by a caveolin-1 dependent mechanism

Biochem Biophys Res Commun. 2005 Nov 25;337(3):849-52. doi: 10.1016/j.bbrc.2005.09.125. Epub 2005 Sep 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caveolin 1 / metabolism*
  • Cells, Cultured
  • Drug Combinations
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Enzyme Activation / drug effects
  • Humans
  • Insulin / administration & dosage*
  • Insulin-Like Growth Factor I / administration & dosage*
  • Nitric Oxide Synthase Type III / metabolism*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • Caveolin 1
  • Drug Combinations
  • Insulin
  • Insulin-Like Growth Factor I
  • Nitric Oxide Synthase Type III