Attenuation of Diabetes-Induced Defects in Cardiac Sarcoplasmic Reticulum and Myofibrils by Propionyl L-Carnitine Therapy

Our previous work showed that treatment of diabetic rats with propionyl L-carnitine (PPLC), a metabolic intervention, improved cardiac function and depressed the occurrence of Ca2+-overload in addition to attenuating sarcolemmal defects in Na+-K+ ATPase, Na+-Ca2+ exchange and Ca2+/Mg2+-ecto ATPase activities. This study was undertaken to examine the efficacy of PPLC treatment on changes in sarcoplasmic reticulum (SR) Ca2+-uptake and Ca2+-stimulated ATPase as well as myofibril (MF) Ca2+-ATPase activities by employing male Sprague-Dawley rats injected with streptozotocin (65 mg/kg) for the induction of diabetes. Three days after inducing diabetes, diabetic rats were treated with or without PPLC (250 mg/kg/day) for 8 weeks. PPLC treatment was observed to improve cardiac function and attenuate depressions in both SR Ca2+-uptake and Ca2+-pump ATPase activities without affecting depressions in MF Ca2+-stimulated or Mg2+-ATPase activities as well as myosin Ca2+- or actin-stimulated ATPase activities in diabetic hearts. PPLC treatment also reduced the increased content of cardiac long-chain acylcarnitine as well as the plasma levels of free fatty acids and triglycerides without affecting the elevated levels of plasma glucose or depressed levels of plasma insulin in diabetic animals. The depression in cardiac carnitine content was corrected by PPLC treatment. Under in vitro conditions, palmitoyl L-carnitine (PMLC; a long-chain acylcarnitine) did not affect MF Ca2+-stimulated ATPase in the absence or presence of PPLC, whereas the inhibitory effect of PMLC on SR Ca2+-stimulated ATPase activities was antagonized by PPLC. These data suggest that the beneficial effects of PPLC in diabetic cardiomyopathy may be associated with attenuation of SR Ca2+-handling defects rather than with any action regarding depressed MF ATPase activity.