IGF-I/insulin hybrid receptors in human endothelial cells

Vascular complications are common in diabetes. IGF-I receptors (IGF-IR) and insulin receptors (IR) in endothelial cells might respond to altered levels of IGF-I and insulin, resulting in altered endothelial function in diabetes. We therefore studied IGF-IR and IR gene expression. ligand binding, receptor protein. and phosphorylation in human umbilical vein endothelial cells (HUVEC). IGF-IR mRNA was more abundant than IR mRNA in freshly isolated HUVEC (IGF-IR/IR ratio 7.1 +/- 1.5) and in cultured HUVEC(ratio 3.5 +/- 0.51). Accordingly, specific binding of I-125-IGF-I (0.64 +/- 0.25%) was higher than that of I-125-insulin (0.25 +/- 0.09%). Protein was detected for both receptors and IGF-I/insulin hybrid receptors. IGF-IR phosphorylation was stimulated by 10(-10) to 10(-8) M IGF-I. IR were activated by 10(-9) to 10(-8) M insulin and IGF-I. We conclude that HUVEC express more IGF-IR than IR. and also express hybrid receptors. Both IGF-I and insulin phosphorylate their own receptors but only IGF-I seems to phosphorylate hybrid receptors. (C) 2004 Elsevier Ireland Ltd. All rights reserved.