Effects of hyperinsulinemia on plasma levels of circulating adhesion molecules.
Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), a potential cardiovascular risk factor, are increased in diabetics. Among other factors, hyperinsulinemia has been proposed to enhance its release into the circulation. Thus, we directly examined the effects of insulin infusion on plasma levels of circulating adhesion molecules, and two other endothelial markers, i.e. von Willebrand factor (vWF) and soluble thrombomodulin (sTM). The study design was balanced, randomized, placebo-controlled, double blind, and cross-over. Twelve healthy male subjects received, on separate study days, a euglycemic hyperinsulinemic clamp (3 mU/kg x min) or placebo over 6 h. Plasma levels of cICAM-1, vascular cell adhesion molecule-1, circulating E-selectin, and sTM were measured by enzyme immunoassay; vWF-Ag was measured using a STA clot analyzer. Plasma levels of these adhesion molecules and endothelial cell activation markers were not affected despite a 30-fold increase in insulin levels. Hyperinsulinemia has no adverse effect on circulating ICAM-1, vascular cell adhesion molecule-1, E-selectin, vWF, or sTM and therefore does not directly induce endothelial activation.
Jilma
B
B
Department of Clinical Pharmacology-TARGET, Vienna University Hospital School of Medicine, Wien, Austria. bernd.jilma@univie.ac.at
Dallinger
S
S
Hergovich
N
N
Eichler
H G
HG
Richter
V
V
Wagner
O F
OF
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D018180:Thrombomodulin / Q000097:blood; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D007328:Insulin; D010456:Peptides, Cyclic; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; C072247:cyclo(Trp-Asp-Pro-Val-Leu)