C-peptide inhibits leukocyte-endothelium interaction in the microcirculation during acute endothelial dysfunction

C-peptide is a cleavage product that comes from processing proinsulin to in sulin that induces nitric oxide (NO) -mediated vasodilation, NO modulates l eukocyte-endothelium interaction. We hypothesized that C-peptide might inhi bit leukocyte-endothelium interaction via increased release of endothelial NO, Using intravital microscopy of the rat mesentery, we measured leukocyte -endothelium interactions after administration of C-peptide to the rat. Sup erfusion of the rat mesentery with either thrombin or L-NAME consistently a nd significantly increased the number of rolling, adhering, and transmigrat ed leukocytes, C-peptide significantly attenuated either thrombin- or L-NAM E-induced leukocyte-endothelium interactions in rat mesenteric venules. A c ontrol scrambled sequence of C-peptide characterized by the same amino acid composition in a randomized sequence failed to inhibit leukocyte-endotheli um interactions. These effects of C-peptide were associated with decreased surface expression of the cell adhesion molecules P-selectin and ICAM-1 on the microvascular endothelium. Endothelial nitric oxide synthase (eNOS) mRN A levels were increased in rats injected with C-peptide. This enhanced eNOS expression was associated with a marked increase in basal NO release from the aorta of C-peptide-treated rats. We conclude that C-peptide is a potent inhibitor of leukocyte-endothelium interaction and that this effect is spe cifically related to inhibition of endothelial cell adhesion molecules via maintenance of NO release from the vascular endothelium.-Scalia, R., Coyle, K. M., Levine, B, J., Booth, G., Lefer, A. M. C-peptide inhibits leukocyte -endothelium interaction in the microcirculation during acute endothelial d ysfunction.