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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/E1124    most recent 00565.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Johansson, G. S. Articles by Arnqvist, H. J. Search for Related Content PubMed PubMed Citation Articles by Johansson, G. S. Articles by Arnqvist, H. J.

Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells

¹Department of Biomedicine and Surgery, Division of Cell Biology; and ²Diabetes Research Centre, Faculty of Health Sciences, Linköping University, Linköping, Sweden

Submitted 18 November 2005 ; accepted in final form 20 June 2006

Insulin and insulin-like growth factor I (IGF-I) are known to affect cardiovascular disease. We have investigated ligand binding and the dose-response relationship for insulin and IGF-I on vascular smooth muscle cells (VSMCs) at the receptor level. VSMCs from rat thoracic aorta were serum starved, stimulated with IGF-I or insulin, lysed, immunoprecipitated, and analyzed by Western blot. D-[U-¹⁴C]Glucose accumulation and [6-³H]thymidine incorporation into DNA were also measured. Specific binding of both insulin and IGF-I was demonstrated, being higher for IGF-I. Both IGF-I receptor (IGF-IR) and insulin receptor (IR) -subunits were detected and coprecipitated after immunoprecipitation (IP) against either of the two. No coprecipitation was found after reduction of disulphide bonds with dithiotreitol before IP. After stimulation with 10^–10–10^–9 M IGF-I, IP of the IGF-IR, or IR -subunit and immunoblot with anti-phosphotyrosine antibody, we found two distinct bands indicating phosphorylation of both the IGF-IR and the IR -subunit. Stimulation with 10^–10–10^–9 M insulin and IP against the IGF-IR did not show phosphorylation of either -subunit, whereas after IP of the IR we found phosphorylation of the IR -subunit. [¹⁴C]Glucose accumulation and [³H]thymidine incorporation were elevated in cells stimulated with IGF-I at 10^–10–10^–7 M, reaching maximum by 10^–9 M. Insulin stimulation showed measurable effects only at supraphysiological concentrations, 10^–8–10^–7 M. In conclusion, coprecipitation of both the IGF-IR and the IR -subunit indicates the presence of hybrid insulin/IGF-I receptors in VSMC. At a physiological concentration, insulin activates the IR but does not affect either glucose metabolism or DNA synthesis, whereas IGF-I both activates the receptor and elicits biological effect.

insulin-like growth factor I; ligand binding; receptor phosphorylation; immunopreciptation; dexoyribonucleic acid synthesis; glucose metabolism

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