Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators.
Endothelial expression of cell adhesion molecules (CAMs) plays an important role in atherosclerosis. Atherosclerosis is increased in hyperinsulinemic states, but whether insulin per se is proatherogenic remains unclear. To investigate the effects of hyperinsulinemia on CAM expression, plasma levels of ICAM-1, VCAM-1 and E-selectin were measured before and after forearm infusion of insulin in healthy subjects. Insulin administration for 2h resulted in significant hyperinsulinemia, whereas no significant change was observed in soluble CAMs (all p > 0.05). Because insulin stimulates endothelial release of both endothelin-1 (ET-1) and nitric oxide (NO), which may modulate the expression of CAMs, we also investigated the response of CAMs to ET-1 receptor blockade, alone and in combination with NO synthesis inhibition. ET-1 receptor blockade during hyperinsulinemia resulted in a vasodilator response, but did not affect soluble CAMs (all p > 0.05). Superimposition of NO inhibition by L-NMMA reversed the vasodilator effect of ET-1 blockade, without affecting soluble CAMs (all p > 0.05). In conclusion, acute hyperinsulinemia, alone or during ET-1 and NO pathway blockade, does not affect soluble CAMs. These results do not support a direct effect of insulin on endothelial cells to affect leukocyte adhesiveness to the vascular wall.
Cardillo
Carmine
C
National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
Mettimano
Marco
M
Mores
Nadia
N
Koh
Kwang K
KK
Campia
Umberto
U
Panza
Julio A
JA
D015415:Biomarkers / Q000097:blood; D019040:E-Selectin / Q000097:blood / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D015415:Biomarkers; D019040:E-Selectin; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019323:omega-N-Methylarginine; D009569:Nitric Oxide