Human microvascular endothelial cells are sensitive to IGF-I but resistant to insulin at the receptor level
2008 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, Vol. 296, no 1-2, 58-63 p.Article in journal (Refereed) Published
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.
propagation downstream. The IGF-IR β-subunit and the IR β-subunitwere detected and found to co-precipitate. IRAwas themajor IR isoformexpressed in HMVEC. IGF-I 10−9 to 10−8M phosphorylated its cognate receptor β-subunit. IGF- I also phosphorylated the IR β-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 10−7M and by insulin 10−7M. IGF-I at 10−8 to 10−6M 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.
Place, publisher, year, edition, pages
2008. Vol. 296, no 1-2, 58-63 p.
IGF-I receptor, Insulin receptor, Hybrid receptor, RT-PCR, Western blot, Thymidine incorporation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-16347DOI: 10.1016/j.mce.2008.07.012OAI: oai:DiVA.org:liu-16347DiVA: diva2:133964