title: Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells.
abstract: Micro- and macroangiopathy are major causes of morbidity and mortality in patients with diabetes. Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. Cultured human dermal microvascular endothelial cells (HMVEC) and human aortic endothelial cells (HAEC) were used. Gene expression was measured by quantitative real-time RT-PCR and receptor protein by ligand-binding assay. Phosphorylation of IGF-IR beta-subunit was analyzed by immunoprecipitation and Western blot. Glucose metabolism and DNA synthesis was assessed using [(3)H]glucose and [(3)H]thymidine incorporation, respectively. We detected gene expression of IGF-IR and IR in HAEC and HMVEC. IGF-IR gene expression was severalfold higher than that of IR. The specific binding of (125)I-IGF-I was higher than that of (125)I-insulin in HAEC and HMVEC. Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. Human micro- and macrovascular endothelial cells express more IGF-IR than IR. IGF-I and high concentrations of glargine and insulin activates the IGF-IR. Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo.
authors.affiliation: Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden.
authors.forename: Simona I
authors.initials: SI
authors.lastname: Chisalita
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Arnqvist
mesh_terms: D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008833:Microcirculation; D011233:Precipitin Tests; D011869:Radioligand Assay; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005947:Glucose; D013936:Thymidine