Platelet glutathione and thromboxane synthesis in diabetes

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 +/- 0.73 microgram/10(9) platelets, mean +/- SD) was significantly (P less than 0.001) lower than in platelets from control subjects (10.10 +/- 1.58 microgram/10(9) platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P less than 0.001) more TXB2 was formed in PRP from diabetic subjects (344 +/- 87 ng/2.5 X 10(8) platelets) than in PRP from control subjects (132 +/- 35 ng/2.5 X 10(8) platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 +/- 117 pg/ml) in comparison with control subjects (187 +/- 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.