Platelet function and acetyl-coenzyme A metabolism in type 1 diabetes mellitus.

Blood platelets take up glucose through insulin-independent GLUT-3 transporter. It is, however, unclear how diabetes affects further steps of glucose and glucose-derived acetyl-coenzyme A (CoA) metabolism in platelets. There is no evidence to explain whether these changes are linked to the disease-induced disturbances in platelet function. We found that activities of some key enzymes of glucose and acetyl-CoA metabolism in platelets were elevated in diabetes. Activities of hexokinase, pyruvate dehydrogenase and ATP-citrate lyase in diabetic platelets were found to be increased by 53, 56 and 88%, respectively. Accordingly, diabetes brought about 86% increase of platelet acetyl-CoA and activation of malonyl dialdehyde synthesis as well as spontaneous and thrombin-induced platelet aggregation by about 56, 50 and 15%, respectively. Significant correlations have been observed between some parameters of acetyl-CoA metabolism, platelet function and serum fructosamine in diabetic patients but not in healthy individuals. Our findings indicate that increased platelet activity in diabetic subjects may, at least in part, result from chronic hyperglycaemia-induced changes in acetyl-CoA metabolism, yielding an increase in its concentration in platelets.