Broderick T L, Haloftis G, Paulson D J
Midwestern University, Department of Physiology, Downers Grove, Illinois, USA.
J Mol Cell Cardiol. 1996 Feb;28(2):331-40. doi: 10.1006/jmcc.1996.0031.
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.
本研究旨在确定L-丙酰肉碱(LPC)治疗是否有助于预防慢性糖尿病患者心脏功能衰退。通过尾静脉注射链脲佐菌素(60mg/kg)诱导糖尿病。两周后,开始治疗,在饮水中补充浓度为1mg/ml的LPC。经过6周的治疗期后,在离体工作心脏中测定心肌底物利用情况和心脏功能。在另一组心脏中,还测定了LPC治疗对线粒体呼吸的影响。结果显示,与对照组相比,糖尿病心脏氧化葡萄糖的速率要低得多,但氧化棕榈酸的速率相似。糖尿病与对照组相比的影响还表现为心脏泵功能显著下降。然而,用LPC治疗后,糖尿病心脏氧化葡萄糖和棕榈酸的速率显著增加,心脏泵功能显著改善。此外,LPC治疗可预防糖尿病患者出现的心脏线粒体呼吸抑制。我们的研究结果表明,长期LPC治疗可预防糖尿病引起的心脏泵功能衰退。这种有益作用的可能机制包括葡萄糖和脂肪酸代谢在能量方面的有利转变。