Induction of Ca-independent PLA(2) and conservation of plasmalogen polyunsaturated fatty acids in diabetic heart

Diabetes-induced changes in phospholipase A(2) (PLA(2)) activity have been measured in several tissues but are undefined in diabetic myocardium. We me asured ventricular PLA(2) activity in control, streptozotocin-induced diabe tic, and insulin-treated diabetic rats and characterized myocardial phospho lipids to determine whether diabetes altered myocardial phospholipid metabo lism. Increased membrane-associated Ca2+-independent PLA(2) (iPLA(2)) activ ity was observed in diabetes that was selective for arachidonylated phospho lipids. Increased iPLA(2) activity was accompanied by an increase in cholin e lysophospholipids. Diabetes was associated with marked alterations in the phospholipid composition of the myocardium, characterized by decreases in esterified arachidonic and docosahexaenoic acids and increases in linoleic acid. The decrease in polyunsaturated fatty acids was confined to diacylpho spholipids, whereas the relative amount of these fatty acids in plasmalogen s was increased. Diabetes-induced changes in PLA(2) activity, lysophospholi pid production, and alterations in phospholipid composition were all revers ed by insulin treatment of diabetic animals. Diabetesinduced changes in mem brane phospholipid content and phospholipid hydrolysis may contribute to so me of the alterations in myocardial function that are observed in diabetic patients.