Enhanced Platelet Sensitivity to IGF-1 in Patients with Type 2 Diabetes Mellitus.

Abstract

Diabetes mellitus is characterized by increased platelet activation which is determined by many factors including changes in the expression of membrane proteins. The aim of this study was to investigate the sensitivity of human platelets to the insulin-like growth factor (IGF) system in patients with poorly controlled type 2 diabetes mellitus (DM2). Ligand binding was analyzed using 125I-labelled IGF-1 and insulin, and relative expression of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) was evaluated by Western blotting. Platelet aggregation in the presence of IGF-1 was studied by the plate aggregometry assay. We found that platelets from DM2 patients exhibited significantly higher IGF-1 binding and upregulation of IGF-1R expression in comparison with healthy individuals. Both insulin binding and IR expression were lower in the DM2 group, but the differences with the healthy control were statistically insignificant. The potentiating effect of IGF-1 on the thrombin-induced activation of platelets was detected in both groups but was significantly more pronounced in the DM2 patients. The initial rate of platelet activation in the presence of IGF-1 positively correlated with the concentration of glycated hemoglobin. Platelets isolated from DM2 patients displayed elevated expression of the IGF-1R subunits, which might have contributed to the higher sensitivity of these cells to IGF-1 in thrombin-initiated aggregation by increasing the rate of platelet activation. However, further experiments are needed to investigate the role of IGF-1 in thrombotic complications that usually accompany diabetes.