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 μg/109 platelets, mean ± SD) was significantly (P < 0.001) lower than in platelets from control subjects (10.10 ± 1.58 μg/109 platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P < 0.001) more TXB₂ was formed in PRP from diabetic subjects (344 ± 87 ng/2.5 × 10⁸ platelets) than in PRP from control subjects (132 ± 35 ng/2.5 × 10⁸ 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.