Receptors for insulin and insulin-like growth factor I (IGF-I) have been identified in endothelial cells derived from micro- and macrovessels. The insulin receptor in endothelial cells is structurally similar to that in other cell types and activation of its receptor tyrosine kinase leads to phosphorylation of insulin receptor substrate-1. In endothelial cells, insulin mediated activation of phosphatidylinositol 3-kinase (PI3K), Akt (protein kinase B)and the mitogen-activated protein kinase (ERK1/2) pathway is associated with an increase in eNOS gene expression, NO release and transport of L-arginine the physiological precursor for NO. Short-term and long-term actions of insulin on the endothelial L-arginine-nitric oxide signalling pathway will be reviewed.
Supported by Wellcome Trust, BHF and MRC.
22 - 24 Mar 2004
British Endocrine Societies