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Horm Metab Res 2008; 40(9): 588-592
DOI: 10.1055/s-0028-1082325
Review

© Georg Thieme Verlag KG Stuttgart · New York

The Role of IGF-system in Vascular Insulin Resistance

H. J. Arnqvist 1 , 2
  • 1Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  • 2Diabetes Research Centre, Faculty of Health Sciences, Linköping University, Linköping, Sweden
Further Information

Publication History

received 02.10.2007

accepted 23.01.2008

Publication Date:
15 September 2008 (online)

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Abstract

Insulin and IGF-I are closely related peptides, which interact by several mechanisms. In high supraphysiological concentrations (≥10−8 M), they cross-react with each other's receptors with 100- to 1000-fold lower affinity than with their cognate receptors. This can cause confusion, since in many in vitro studies, insulin has been used in high unphysiological concentrations, which activate IGF-I receptors. Due to the differences in affinity, insulin and IGF-I probably do not activate each other's receptors in vivo. IGF-I receptors are several-fold more abundant than insulin receptors in human micro- and macrovascular endothelial cells and in human vascular smooth muscle cells. Both insulin and IGF-I receptor protein can be demonstrated and they are activated by their cognate ligand at physiological concentrations of 10−9–10−10 M. In vascular smooth muscle cells, IGF-I but not insulin stimulates metabolism and growth. IGF-I stimulates DNA-synthesis and growth in microvascular endothelial cells, but neither insulin nor IGF-I have any effect on macrovascular endothelial cells. Both insulin and IGF-I have been shown to stimulate nitric oxide production in endothelial cells, but only the effect of IGF-I was obtained at a physiological concentration. In both endothelial and vascular smooth muscle cells, insulin and IGF-I receptors occur as insulin/IGF-I hybrid receptors with high affinity to IGF-I and low for insulin. Due to the low number of insulin receptors and the presence of hybrid receptors the insulin receptor signal is probably too attenuated to elicit biological effects, explaining the insulin resistance of vascular cells in vitro. In vivo both insulin and IGF-I have been reported to increase muscle blood flow in physiological concentrations. Whether this is due to direct effects on endothelial cells or indirectly induced is not clear. The effect of insulin is attenuated by insulin resistance. In conclusion, the in vitro data suggest that endothelial cells and vascular smooth muscle cells are sensitive to IGF-I, but insensitive to insulin, and this is due to a preponderance of IGF-I receptors and the presence of insulin/IGF-I hybrid receptors.

Key words

endothelial cells - vascular smooth muscle - insulin - IGF-1 receptors

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Correspondence

H. J. ArnqvistMD, PhD 

Department of Clinical and Experimental Medicine

Division of Cell Biology

University Hospital

581 85 Linköping

Sweden

Phone: +46/13/22 27 89

Fax: +46/13/22 42 73

Email: hans.arnqvist@ibk.liu.se

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