Metabolism of palmitate in isolated working hearts from spontaneously diabetic 'BB' Wistar rats

Abstract

Myocardial fatty acid metabolism was studied in spontaneously-diabetic 'BB' Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of 'BB' Wistar rats, insulin-treated diabetic 'BB' rats, and diabetic 'BB' rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (1-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 ± 0.043 and 0.528 ± 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 ± 0.032 and 0.629 ± 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals were accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 ± 0.3 μmol/g dry wt/30 min versus 4.8 ± 0.3, 5.9 ± 0.7, and 5.7 ± 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 ± 25 nmol/g dry wt versus 484 ± 27, 508 ± 56, and 534 ± 9, in treated diabetic, nondiabetic, and control rats, respectively). Combined with earlier studies in which high coenzyme A levels in control hearts also resulted in an increased rate of palmitate incorporation into triglycerides, the data suggest that high levels of myocardial coenzyme A contribute to the accumulation of myocardial triglycerides seen in poorly controlled diabetes. Similarly, contrary to earlier reports, a decrease in the rate of fatty acid oxidation was not observed in diabetic rat hearts.