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Am J Physiol Endocrinol Metab (January 13, 2004). doi:10.1152/ajpendo.00327.2003
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Submitted on July 15, 2003
Accepted on January 5, 2004

Insulin-like growth factor-I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells

Simona I. Chisalita1 and Hans J. Arnqvist2*

1 Division of Cell Biology, Department of Biomedicine and Surgery, Linkoping University, Linkoping, Sweden
2 Division of Cell Biology, Department of Biomedicine and Surgery, Linkoping University, Linkoping, Sweden; Division of Internal Medicine, Department of Medicine and Care, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden

* To whom correspondence should be addressed. E-mail: hans.arnqvist{at}ibk.liu.se.

Aim. Micro- and macroangiopathy are major causes of morbidity and mortality in patients with diabetes. Our aim was to characterize IGF-IR and IR in human micro- and macrovascular endothelial cells. Methods. 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 3H-glucose and 3H-thymidine incorporation, respectively. Results. We detected gene expression of IGF-IR and IR in HAEC and HMVEC. IGF-IR gene expression was several folds higher than that of IR. The specific binding of 125I-IGF-I was higher than that of 125I-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 (10-8M) and insulin (10-6M) and in HMVEC for IGF-I and glargine (10-8M, 10- 6M). IGF-I 10-7M stimulated incorporation of 3H-thymidine into DNA, and at a concentration of 10-9-10-7M also the incorporation of 3H-glucose in HMVEC, whereas glargine and insulin had no significant effects at concentrations of 10-9-10-7M. Conclusion. 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.




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