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This Article Accepted manuscript (PDF) All Versions of this Article: JME-09-0021v1 43/6/231    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chisalita, S. Articles by Arnqvist, H. PubMed PubMed Citation Articles by Chisalita, S. Articles by Arnqvist, H.

S Chisalita, Department of clinical and experimental medicine, Linköping University, Cellbiology and Diabetes Research Centre, Linköping, Sweden
G Johansson, Department of clinical and experimental medicine, Linköping University, Cellbiology and Diabetes Research Centre, Linköping, Sweden
E Liefvendahl, Department of clinical and experimental medicine, Linköping University, Cellbiology and Diabetes Research Centre, Linköping, Sweden
K Bäck, Department of clinical and experimental medicine, Linköping University, Cellbiology and Diabetes Research Centre, Linköping, Sweden
H Arnqvist, Department of clinical and experimental medicine, Linköping University, Cellbiology and Diabetes Research Centre, Linköping, Sweden

Correspondence: Hans Arnqvist, Email: hans.arnqvist{at}liu.se

Abstract

Whether insulin, in physiological concentrations, has direct effects on VSMCs, remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, effects of IGF-I and IGF-II were also studied. Cultured human aortic smooth muscle cells (HASMC) were used. Receptor mRNA was analysed by quantitative RT-PCR and receptor protein by ELISA and Western Blot. The biological effects were studied by thymidine incorporation and glucose accumulation.

In HASMC both mRNA and protein expression of IGF-I receptors (IGF-IR) were 5 fold higher compared to insulin receptor (IR). IR isoform A mRNA was 13 times more expressed than IR isoform B. IR and IGF-IR coprecipitated indicating the presence of hybrid IR/IGF-IR. Phosphorylation of the IGF-IR beta-subunit was obtained by IGF-I 10-9-10-8mol l-1 and IGF-II 10-8mol l-1. IR beta-subunit was phosphorylated by IGF-I 10-8mol l-1 but not by insulin. IGF-I stimulated IRS-I at 10-8mol l-1, Akt and Erk 1/2 at 10-9-10-8mol l-1, respectively. IGF-II stimulated Akt at 10-8mol l-1 whereas insulin had no effect. IGF-I and IGF-II at a concentration of 10-8-10-7mol l-1 significantly stimulated 3H-thymidine incorporation, whereas insulin did not. 14C-Glucose accumulation was stimulated by IGF-I or IGF-II 10-8-10-7mol l-1, and also by insulin 10-7mol l-1.

Our results suggest that IGF-IR and hybrid IR/IGF-IR are activated by physiological concentrations of IGF-I and IGF-II in HASMC and this causes downstream signaling and biological effects, while insulin has no effect on its receptor or downstream signaling probably due to a preponderance of IGF-IR and incorporation of IR into hybrid IR/IGF-IR.