Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2
2009 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, Vol. 43, no 5-6, 231-239 p.Article in journal (Refereed) Published
Whether insulin, in physiological concentrations, has direct effects on vascular smooth muscle cells (VSMC) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, effects of insulin-like growth factor (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. Immunoprecipitation and Western blot showed co precipitation of IR and IGF-IR indicating the presence of hybrid IR/IGF-IR.
Phosphorylation of the IGF-IR β-subunit was obtained by IGF-I 10-9-10-8mol l-1 and IGF-II 10-8mol l-1. IR β-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.
Place, publisher, year, edition, pages
2009. Vol. 43, no 5-6, 231-239 p.
Receptors, insulin, IGF-I, IGF-II, IRS-1, Erk 1/2, Akt, DNA-synthesis, glucose accumulation.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-19283DOI: 10.1677/JME-09-0021OAI: oai:DiVA.org:liu-19283DiVA: diva2:224049