title: Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects.
abstract: 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-α 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-α has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.
authors: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, S-581 85 Linköping, Sweden.
authors: Karolina
authors: K
authors: Bäck
authors: Rakibul
authors: R
authors: Islam
authors: Git S
authors: GS
authors: Johansson
authors: Simona I
authors: SI
authors: Chisalita
authors: Hans J
authors: HJ
authors: Arnqvist
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011972:Receptor, Insulin / Q000819:agonists / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin