Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects
2012 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 0022-0795, Vol. 215, no 1, 89-96 p.Article in journal (Refereed) Published
Diabetes is associated with microcirculatory dysfunction and heart failure and changes in insulin and IGF1 levels. Whether human cardiac microvascular endothelial cells (HMVEC-Cs) are sensitive to insulin and/or IGF1 is not known. We studied the role of insulin receptors (IRs) and IGF1 receptors (IGF1Rs) in metabolic, mitogenic and anti-inflammatory responses to insulin and IGF1 in HMVEC-Cs and human umbilical vein endothelial cells (HUVECs). IR and IGF1R gene expression was studied using real-time RT-PCR. Receptor protein expression and phosphorylation were determined by western blot and ELISA. Metabolic and mitogenic effects were measured as glucose accumulation and thymidine incorporation. An E-selectin ELISA was used to investigate inflammatory responses. According to gene expression and protein in HMVEC-Cs and HUVECs, IGF1R is more abundant than IR. Immunoprecipitation with anti-IGF1R antibody and immunoblotting with anti-IR antibody and vice versa, showed insulin/IGF1 hybrid receptors in HMVEC-Cs. IGF1 at a concentration of 10(-8) mol/l significantly stimulated phosphorylation of both IGF1R and IR in HMVEC-Cs. In HUVECs IGF1 10(-8) mol/l phosphorylated IGF1R. IGF1 stimulated DNA synthesis at 10(-8) mol/l and glucose accumulation at 10(-7) mol/l in HMVEC-Cs. TNF-alpha dramatically increased E-selectin expression, but no inflammatory or anti-inflammatory effects of insulin, IGF1 or high glucose were seen. We conclude that HMVEC-Cs express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors. TNF-alpha has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.
Place, publisher, year, edition, pages
Society for Endocrinology , 2012. Vol. 215, no 1, 89-96 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-86558DOI: 10.1530/JOE-12-0261ISI: 000309000000010OAI: oai:DiVA.org:liu-86558DiVA: diva2:579069