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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
-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
-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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