3-bromopyruvate affects blood platelets responses in type 2 diabetes.

Hyperactivity of blood platelets is an essential factor in pathomechanism of diabetes-evoked angiopathies. The aim of this work was to investigate whether blood platelets hyperactivity resulting from type 2 diabetic hyperglycaemia-increased pyruvate dehydrogenase complex activity and excessive acetyl-CoA accumulation may be brought to the normal range by the enzyme inhibitors. Platelets were isolated from blood of 9 type 2 diabetic patients and 10 healthy donors. Effects of 3-bromopyruvate and 3-nitropropionate on pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase activities, as well as levels of acetyl-CoA, ATP, thiobarbituric acid reactive species and aggregation were assessed in non-activated and thrombin-activated platelets. In type 2 diabetic patients fasting plasma glucose and fructosamine levels were 61, 64%, respectively higher than in the healthy group (p<0.001). In non-activated diabetic platelets PDHC activity, PDHC-E2, acetyl-CoA and ATP levels were 66, 70, 68 and 60%, respectively higher than in platelets from healthy controls (p<0.01). 3-bromopyruvate (0.1mM) decreased pyruvate dehydrogenase activity in healthy and diabetic platelets by 42% and 59%, respectively. Similar inhibitory effects were observed for acetyl-CoA and ATP levels, aggregation and TBARS accumulation rates. Succinate dehydrogenase activity was inhibited by 3-nitropropionate (10mM) to 38 and 41% of control values in healthy and diabetic platelets, respectively but affected neither function nor acetyl-CoA metabolism in platelets of both groups. These data indicate that inhibition of pyruvate dehydrogenase excessive activity in diabetic platelets by 3-bromopyruvate may normalize their functional parameters though adjustment of acetyl-CoA/ATP levels to control values.