Improvement of myocardial function and metabolism in diabetic rats by the carnitine palmitoyl transferase inhibitor Etomoxir.
The effect of Etomoxir as a carnitine palmitoyl transferase I-inhibitor was investigated in normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 8 days by intraperitoneal injection in order to inhibit the oxidation of fatty acids and to increase the metabolism of glucose. This carnitine palmitoyl transferase I-inhibitor significantly improved and almost normalized the decreased heart function in chronic diabetic rats. Additionally to the improvement of ventricular heart function, alterations in the conducting system of the diabetic heart were significantly ameliorated. The serum concentrations of glucose, glycerol, cholesterol, tricylglycerol, phospholipids, and beta-hydroxybutyrate were significantly lower in comparison to untreated diabetic animals, while the serum concentration of free fatty acids markedly increased. In addition to the improvement of ventricular heart function, the carnitine content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased significantly. Thus, Etomoxir may be valuable not only as a potential anti-diabetic drug but also as a lipid-lowering agent for the treatment of diabetic related dyslipoproteinaemias and, in addition, as an agent in the treatment of diabetic cardiomyopathy. However, a long-term evaluation of the metabolic consequences of the blocked carnitine palmitoyltransferase I is necessary.
Schmitz
F J
FJ
Diabetes Research, Department of Clinical Biochemistry, Dusseldorf, Germany.
Rösen
P
P
Reinauer
H
H
D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D007004:Hypoglycemic Agents; D013311:Streptozocin; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; C054207:etomoxir; D002331:Carnitine