Acute Hyperglycaemia Enhances Platelet Activation: Involvement of Multiple Mechanisms.

Diabetes mellitus is associated with platelet dysfunction, and hypoglycemic treatments may counteract this diabetic alteration. We thus studied how acute hyperglycemia influences platelet function. Fast blood (n=20) was incubated with different levels of glucose (5, 15, and 30 mM) for 5 min, and without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry, while platelet aggregation was also measured using impedance aggregometry. Blood glucose levels had little influence on unstimulated platelets. Hyperglycemia enhanced ADP- and TRAP-induced platelet P-selectin expression. Hyperglycemia also increased TRAP-induced platelet fibrinogen binding. High glucose levels mildly increased ADP- and TRAP-induced platelet-leukocyte aggregation. The blockade of protein kinase C (PKC) slightly attenuated ADP-induced, and markedly inhibited TRAP-induced platelet activation. PKC blockade had, however, little effect on hyperglycemia effect. Platelet P-selectin expression induced by the direct PKC activator phorbol 12-myristate 13-acetate (PMA) was not augmented by hyperglycemia. Superoxide anion scavenging by superoxide dismutase (SOD) reduced, whistle cyclo-oxygenase (COX) inhibition by naproxen did not reduced the enhancing effect of platelet activation by hyperglycemia. In conclusion, acute hyperglycemia enhances platelet activation in whole blood. Superoxide anions contribute importantly to hyperglycemia-enhanced platelet activation, while other mechanisms not identified presently also contribute to hyperglycemic effects.