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Insulin/IGF‐1 hybrid receptor expression on human platelets: consequences for the effect of insulin on platelet function
Author(s) -
HUNTER R.W.,
HERS I.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03637.x
Subject(s) - platelet , insulin , insulin receptor , function (biology) , human insulin , receptor , medicine , endocrinology , platelet activation , biology , microbiology and biotechnology , insulin resistance
Summary. Objectives : As platelets express both insulin and insulin‐like growth factor‐1 (IGF‐1) receptors, their subunits may randomly heterodimerize to form insulin/IGF‐1 receptor hybrids, which avidly bind IGF‐1, but not insulin. This study investigated the possibility that platelets express hybrid receptors, which may affect insulin action on platelet function. Methods : Platelets were incubated with insulin and IGF‐1. Expression and phosphorylation of insulin/IGF‐1 receptors was determined by western blotting of immunoprecipitates, and compared with platelet functional responses. Relative expression of insulin and IGF‐1 receptors was estimated by competitive ligand binding and quantitative polymerase chain reaction. Results : We demonstrated the presence of insulin/IGF‐1 hybrid receptors on human platelets by detecting both insulin and IGF‐1 receptor β subunits in coimmunoprecipitation studies. Stimulation of platelets with insulin (1–100 n m ) resulted in tyrosine phosphorylation of insulin receptors, but not of hybrid receptors. High insulin concentrations (50–100 n m ) stimulated weak phosphorylation of IGF‐1 receptors and protein kinase B (Akt), and correlated with moderately increased aggregation and fibrinogen binding, whereas low insulin concentrations (1–10 n m ) had no effect. In contrast, IGF‐1 (1–100 n m ) induced strong phosphorylation of both hybrid and IGF‐1 receptors, and potentiated platelet aggregation and fibrinogen binding. Specific binding of [ 125 I]IGF‐1 (1.08% ± 0.16%) was significantly higher than that of [ 125 I]insulin (0.15% ± 0.03%). Accordingly, IGF‐1 receptor mRNA was more abundant than insulin receptor mRNA (IGF‐1 receptor/insulin receptor ratio 69 ± 3.8). Conclusions : Insulin has minimal effects on platelet function, which can be explained by the relatively low insulin receptor expression levels resulting in the majority of insulin receptor subunits being expressed as insulin/IGF‐1 hybrids.