Altered intracellular calcium and phorbol 12,13-dibutyrate binding to intact platelets in young obese subjects

The study was designed to examine cytosolic free calcium ((Ca2+)i) and phorbol dibutyryl ester binding in intact platelets of young obese subjects as compared with the platelets of age-matched subjects with non-insulin-dependent diabetes mellitus (NIDDM) and those of healthy control subjects. The assay was studied in basal and thrombin-stimulated conditions. The binding parameter of phorbol ester is a criterion for active protein kinase C (PKC) units in the platelet plasma membrane. The resting (Ca2+)i correlated with body mass index (BMI)(r = 0.385, p = 0.0034) and plasma insulin level (r = 0.316, p = 0.0269), and the resting (Ca2+)i level was higher in the obesity group (160.6 +/- 15.8 nmol/L; n = 25) than controls (78.9 +/- 7.6 nmol/L; n = 24, p < 0.0001). Among the obesity and control groups, there was a correlation between BMI and fasting plasma insulin level (r = 0.399, p = 0.0237). Systolic blood pressure correlated with BMI(r = 0.504, p = 0.0005). The mean systolic blood pressure of the obesity group was higher than those of the other two groups. The mean Hill coefficient for thrombin-treated platelets of phorbol dibutyrate binding was higher in the obesity group when compared with healthy controls and the subjects with NIDDM (1.47 +/- 0.21 vs 1.06 +/- 0.16 and 0.99 +/- 0.09, respectively; p < 0.05). In conclusion, young subjects with simple obesity have already developed altered platelet Ca2+ regulation that is usually observed in adult patients with a number of metabolic diseases. These data are interpreted to indicate that a relationship exists between dysregulation of PKC and impaired glucose tolerance that precedes other complications of obesity.