title: Insulin's stimulation of endothelial superoxide generation may reflect up-regulation of isoprenyl transferase activity that promotes rac translocation.
abstract: Recent research demonstrates that statin drugs exert a number of favorable effects on endothelial function, independent of lipid modulation, that appear to be mediated by a partial inhibition of prenylation reactions. Statin-induced suppression of PKC-evoked superoxide production may be attributable to an inhibition of rac prenylation and thus translocation that impedes activation of the membrane-bound NAD(P)H oxidase. Conversely, it is now known that hyperinsulinemia up-regulates prenylation reactions by boosting the activities of isoprenyl transferases. In light of new evidence that hyperinsulinemia stimulates endothelial superoxide production via NAD(P)H oxidase, it is tempting to conclude that up-regulation of rac prenylation is at least partially responsible for this phenomenon. In patients afflicted with insulin resistance syndrome, this adverse impact of hyperinsulinemia may be exacerbated by an excessive free fatty acid flux that activates endothelial PKC - another stimulant of the NAD(P)H oxidase - while impeding insulin-mediated activation of nitric oxide synthase. The resulting imbalance of endothelial nitric oxide and superoxide production may be responsible for much of the excess vascular risk associated with this syndrome.
mesh_terms: D004727:Endothelium / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D021381:Protein Transport; D013481:Superoxides / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D007328:Insulin; D013481:Superoxides; D014166:Transferases; D020744:rac GTP-Binding Proteins