PHOSPHORYLATION OF MYOSIN LIGHT-CHAIN IN RESTING PLATELETS FROM NIDDMPATIENTS IS ENHANCED - CORRELATION WITH SPONTANEOUS AGGREGATION

Platelet function in patients with NIDDM is enhanced. We have found th at spontaneous aggregation (i.e., the formation of small-sized aggrega tes in the absence of agonist stimulation) occurs at a high rate in pl atelets from NIDDM patients. We then investigated basal myosin light c hain 20 (MLC) phosphorylation, which plays a key role in platelet shap e change and aggregation, using a monoclonal antibody against a phosph orylation site (serine 19 residue) in the MLC molecule in platelets fr om these patients. Standard calibration curves obtained from purified MLC or the phosphorylated form of myosin light chain 20 (MLC-P) were l inear within the range of 0-150 ng for MLC and 0-3 ng for MLC-P The am ount of MLC or MLC-P in platelets was estimated, and basal MLC phospho rylation was calculated. Platelets were obtained from 9 young healthy control subjects, 13 age- and sex-matched nondiabetic control subjects , and 13 patients with NIDDM. The basal MLC phosphorylation in platele ts was significantly higher in the NIDDM patients than in the control subjects, irrespective of age. These findings suggest that platelets f rom NIDDM patients are activated in vivo. Platelets obtained from NIDD M patients generated spontaneous aggregation, the degree of which was significantly higher than that in control subjects. Platelet spontaneo us aggregation correlated well with basal MLC phosphorylation. These f indings suggest that increases in basal MLC in platelets may be one fa ctor leading to hyperaggregability of platelets in these patients.