Characterisation of receptors for IGF-I and insulin; evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells

Chisalita, Simona I.; Nitert, Marloes Dekker; Arnqvist, Hans J.

doi:10.1016/j.ghir.2006.06.003

Cited by 26 publications

(21 citation statements)

References 47 publications

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“…Insulin/IGF-I hybrid receptors are present in many different human cell types and tissues (19)(20)(21)(22) and in this study we also found hybrid receptors in human PA and dPA as both the IR and the IGF-IR could be detected on the same Western blot membrane after immunoprecipitation against either receptor. Hybrid receptors have previously been demonstrated in human adipose tissue (19).…”

Section: Dna Synthesissupporting

confidence: 74%

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Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Bäck

Arnqvist

2009

Growth Hormone & IGF Research

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Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCR in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR. GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR were detected in PA, dPA and mAD. During differentiation the ratio of IR to IGF-IR increased severalfold. In PA both the IR and the IGF-IR was phosphorylated by their own ligand at 1 nM and in dPA the activation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10 nM and by IGF-I at 1 nM and 10 nM. DNA synthesis was increased by insulin and IGF-I at 10 nM.In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes.Differentiation is characterized by an increased IR/IGF-IR ratio.

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Section: Dna Synthesissupporting

confidence: 74%

“…Insulin/IGF-I hybrid receptors have been found in several different human tissues, as muscle, fat, kidney (19) and human cell types, including different breast cancer cells (20) and endothelial cells (21,22).…”

Section: Introductionmentioning

confidence: 99%

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Bäck

Arnqvist

2009

Growth Hormone & IGF Research

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“…In adipose tissue both IR-A and IR-B are present (Sesti et al, 1995). We have No effect of insulin at 10 -9 -10 -8 M was found on the phosphorylation of IGF-IR in preadipocytes, but insulin is known to phosphorylate the IGF-IR at higher concentrations (Chisalita et al, 2006). The IR in preadipocytes was phosphorylated in response to insulin at physiological concentrations (10 -9 -10 -8 M).…”

Section: Discussionmentioning

confidence: 65%

Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes – Role of insulin and IGF-I receptors

Bäck

Brännmark

Strålfors

et al. 2011

Molecular and Cellular Endocrinology

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“…Characterisation of cells by quantitative RT-PCR demonstrated that HMVEC-Cs expressed considerably more IGF1R mRNA than IR mRNA. We have previously described this in dermal microvascular cells and in macrovascular endothelial cells (Chisalita & Arnqvist 2004, Nitert et al 2005, Chisalita et al 2006. IGF1R protein could be quantitatively measured by ELISA while IR was below the limit of detection.…”

Section: Discussionmentioning

confidence: 93%

“…they bind IGF1 with high affinity, but not insulin (Soos et al 1993, Slaaby et al 2006. We have reported that IRs and IGF1Rs form insulin/ IGF1 hybrid receptors in human macro-and microvascular endothelial cells (Nitert et al 2005, Chisalita et al 2006, Johansson et al 2008, which could be of importance for insulin sensitivity.…”

Section: Introductionmentioning

confidence: 95%

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

Bäck

Islam

Johansson

et al. 2012

Journal of Endocrinology

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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.

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Characterisation of receptors for IGF-I and insulin; evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells

Cited by 26 publications

References 47 publications

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes – Role of insulin and IGF-I receptors

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

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