SUBCELLULAR ALTERATIONS IN CARDIAC PHOSPHOLIPASE-D ACTIVITY IN CHRONIC DIABETES

Several studies have suggested that myocardial phospholipase D (PLD) a nd its hydrolytic product, phosphatidic acid (PtdOH), may regulate Ca2 + movements and contractile performance of the heart. Since abnormal i ntracellular Ca2+ handling is a major factor of myocardial dysfunction in chronic diabetes, we examined subcellular changes in PLD activity in myocardium from insulin-dependent diabetic rats. Diabetes in rats w as induced by a single i.v. injection of streptozotocin (65 mg/kg body wt) and 8 weeks later the ventricular tissue was processed for the is olation of sarcolemma, sarcoplasmic reticulum and mitochondria. Compar ed to age-matched controls, the sarcolemmal, sarcoplasmic reticular an d mitochondrial PLD activities were significantly depressed in the dia betic animals. The depressed sarcolemmal PLD activity was normalized, whereas the sarcoplasmic reticular and mitochondrial enzyme activities were partially reversed upon treating the 6-week diabetic rats with i nsulin for a period of 2 weeks. These data suggest that the reduction of PLD-derived PtdOH may lead to an impairment in this phospholipid si gnal transduction pathway and subsequent cardiac dysfunction in chroni c diabetes.