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Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
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2012 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 215, no 1, 89-96 p.Article in journal (Refereed) Published
Abstract [en]

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.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-86558DOI: 10.1530/JOE-12-0261ISI: 000309000000010OAI: oai:DiVA.org:liu-86558DiVA: diva2:579069
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06

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Bäck, KarolinaIslam, RakibulJohansson, GitChisalita, Ioana SimonaArnqvist, Hans

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Bäck, KarolinaIslam, RakibulJohansson, GitChisalita, Ioana SimonaArnqvist, Hans
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Cell BiologyFaculty of Health SciencesDepartment of Clinical and Experimental MedicineDepartment of Acute Health CareDepartment of Endocrinology and Gastroenterology UHL
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