Involvement of 1,2-diacylglycerol in improvement of heart function by etomoxir in diabetic rats.
Abnormal lipid metabolism has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. In this study, we measured myocardial lipid levels, including 1,2-diacylglycerol (1,2-DAG) and ceramide (CM), and myocardial function in diabetic rats. We also evaluated the effects of etomoxir (ETM), a carnitine palmitoyl transferase I inhibitor, on diabetic rat hearts from the viewpoints of alterations in lipid second messengers and myocardial function. Rats were injected with streptozotocin (60 mg/kg) to induce diabetes and were treated 5 weeks later with ETM (18 mg/kg) for 8 days. In diabetic rats, heart rate, systolic blood pressure, and fractional shortening were significantly reduced compared with those in controls. Treatment of diabetic rats with ETM ameliorated myocardial dysfunction other than heart rate. Myocardial 1,2-DAG levels in diabetic rats were significantly elevated compared with those in controls, while myocardial CM levels were not. ETM treatment caused an additional increase in myocardial 1,2-DAG levels in diabetic rats, but the CM levels did not change. There was a marked difference in fatty acid pattern of 1,2-DAG between diabetic and ETM-treated diabetic rat hearts. The fatty acids 18:1 and 18:2 were significantly increased and the fatty acids 16:0, 18:0, 20:4, and 22:6 were significantly reduced in ETM-treated diabetic rat hearts. These data suggest 1,2-DAG is involved in ameliorating myocardial dysfunction in diabetic rats and that its source is different between diabetic and ETM-treated diabetic rats. CM is unlikely to be involved in the pathogenesis of diabetic cardiomyopathy or the improvement of cardiac contractility in diabetic rats by ETM.
Internal Medicine II, Nagoya University School of Medicine, Japan. khayas@tsuru.med.nagoya-u.ac.jp
K
K
Hayashi
K
K
Okumura
H
H
Matsui
K
K
Murase
H
H
Kamiya
Y
Y
Saburi
Y
Y
Numaguchi
Y
Y
Toki
T
T
Hayakawa
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002331:Carnitine / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004075:Diglycerides / Q000378:metabolism*; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
C011439:1,2-diacylglycerol; D002518:Ceramides; D004075:Diglycerides; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D013311:Streptozocin; C054207:etomoxir; D002331:Carnitine