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 (125)I-IGF-I (0.64 +/- 0.25%) was higher than that of (125)I-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.
Nitert
Marloes Dekker
MD
Diabetes Research Center and Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden.
Chisalita
Simona I
SI
Olsson
Karolina
K
Bornfeldt
Karin E
KE
Arnqvist
Hans J
HJ
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008024:Ligands; D010766:Phosphorylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D008024:Ligands; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin