L-propionylcarnitine enhancement of substrate oxidation and mitochondrial respiration in the diabetic rat heart.
This study was designed to determine whether L-propionylcarnitine (LPC) treatment is beneficial in preventing the depression in cardiac function from occurring in chronic diabetes. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg). Two weeks later, treatment was initiated by supplementing the drinking water with LPC at the concentration of 1 mg/ml. Following a 6-week treatment period, myocardial substrate utilization and cardiac function were determined in isolated working hearts. In a separate group of hearts, the effects of LPC treatment on mitochondrial respiration were also determined. The results showed that diabetic hearts, compared with those of controls, oxidized glucose at a much lower rate, but oxidized palmitate at a similar rate. The effect of diabetes compared a controls was also characterized by a pronounced decrease in cardiac pump function. Following treatment with LPC, however, there was a marked increase in the rates at which glucose and palmitate were oxidized by diabetic hearts, and a significant improvement in cardiac pump performance. In addition, the depression of cardiac mitochondrial respiration seen in diabetes was prevented with LPC treatment. Our findings show that the depression of cardiac pump function by diabetes can be prevented with chronic LPC treatment. Possible mechanisms for this beneficial effect include an energetically favorable shift in glucose and fatty acid metabolism.
Broderick
T L
TL
Midwestern University, Department of Physiology, Downers Grove, Illinois, USA.
Haloftis
G
G
Paulson
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002952:Citric Acid Cycle / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine