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Mol Cell Endocrinol. 2008 Dec 16;296(1-2):58-63. doi: 10.1016/j.mce.2008.07.012. Epub 2008 Jul 30.

Human microvascular endothelial cells are sensitive to IGF-I but resistant to insulin at the receptor level.

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  • 1Link√∂ping University, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Division of Cell Biology, Link√∂ping, Sweden. git.johansson@ibk.liu.se

Abstract

Human microvascular endothelial cells (HMVEC) are sensitive to IGF-I but insulin resistant and express several times more IGF-I receptors (IGF-IR) than insulin receptors (IR). Our aim was to investigate the mechanism of this insulin resistance in cultured HMVEC by studying receptor activation and signal propagation downstream. The IGF-IR beta-subunit and the IR beta-subunit were detected and found to co-precipitate. IRA was the major IR isoform expressed in HMVEC. IGF-I 10(-9) to 10(-8)M phosphorylated its cognate receptor beta-subunit. IGF-I also phosphorylated the IR beta-subunit at 10(-9)M. Phosphorylation of insulin receptor substrate 1 was obtained by IGF-I 10(-9) to 10(-8)M. Akt was phosphorylated by IGF-I at 10(-8) to 10(-7)M and by insulin 10(-7)M. IGF-I at 10(-8) to 10(-6)M significantly increased DNA-synthesis. We conclude that microvascular endothelial cells are sensitive to IGF-I but resistant to insulin due to a preponderance of IGF-I receptors and sequestration of insulin receptors into insulin/IGF-I hybrid receptors.

[PubMed - indexed for MEDLINE]
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