Chisalita, Simona I., and Hans J. Arnqvist. Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro-and macrovascular endothelial cells. Am J Physiol Endocrinol

Aims/hypothesis: Hyperinsulinaemia and insulin resistance, as well as low IGF-I, have been implicated in the pathogenesis of cardiovascular disease. Little is known about direct effects of IGF-I and insulin on human coronary artery smooth muscle cells (HCASMCs). Our aim was to characterise the expression and function of IGF-I receptor (IGF-IR) and insulin receptor (IR) in HCASMCs. Materials and methods: Cultured HCASMCs were used. mRNA expression was measured by quantitative real-time RT-PCR analysis. Receptor proteins, phosphorylation of β-subunits and the presence of hybrid IR/IGF-IR were analysed by immunoprecipitation and western blotting. DNA synthesis and glucose metabolism were assessed using [

In elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing.

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Objective: There are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors. Design and methods: A total of 851 persons aged 66-81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years. Results and conclusion: Patients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) !40% compared with EF R40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P!0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (PZ0.03). This was significant after adjustment for wellknown CV risk factors and ACE inhibitors (PZ0.03). Conclusions: Our results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality.

The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

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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 antiinflammatory 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 K8 mol/l significantly stimulated phosphorylation of both IGF1R and IR in HMVEC-Cs. In HUVECs IGF1 10 K8 mol/l phosphorylated IGF1R. IGF1 stimulated DNA synthesis at 10 K8 mol/l and glucose accumulation at 10 K7 mol/l in HMVEC-Cs. TNF-a dramatically increased E-selectin expression, but no inflammatory or antiinflammatory 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-a has a pronounced pro-inflammatory effect in HMVEC-Cs, which is not counteracted by insulin or IGF1.