Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide.
Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.
Aljada
A
A
Division of Endocrinology, Diabetes, and Metabolism, State University of New York, Buffalo 14209, USA.
Saadeh
R
R
Assian
E
E
Ghanim
H
H
Dandona
P
P
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002469:Cell Separation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D018799:Intercellular Adhesion Molecule-1; D019335:Nitroarginine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III