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Effects of Hyperinsulinemia on Plasma Levels of Circulating Adhesion Molecules

Department of Clinical Pharmacology-TARGET (B.J., S.D., N.H., H.-G.E.) and Department of Medical and Chemical Laboratory Diagnostics (O.F.W.), Vienna University Hospital School of Medicine, A-1090 Wien, Vienna, Austria; and Department of Clinical Chemistry and Pathobiochemistry, University of Leipzig (V.R.), Leipzig, Germany

Address all correspondence and requests for reprints to: Bernd Jilma, M.D., Department of Clinical Pharmacology-TARGET, The Adhesion Research Group Elaborating Therapeutics, Vienna University Hospital School of Medicine, Währinger Gürtel 18-20, A-1090 Wien, Austria. E-mail: bernd.jilma{at}univie.ac.at

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·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.

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