Influence of carnitine acyltransferase inhibitors on the performance and metabolism of rat cardiac muscle.
The effects of carnitine palmitoyl transferase I inhibitors were studied in isolated perfused rat heart and in in vivo studies with normal and diabetic rats. In isolated perfused rat hearts of acutely diabetic and Zucker rats, clomoxir (sodium 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate) inhibited the oxidation rate of endogenous fatty acids and increased the oxidation rate of glucose. Etomoxir, an analogue of clomoxir, was used in the in vivo studies with normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 6 days by intraperitoneal injection. This carnitine palmitoyl transferase inhibitor significantly ameliorated the decreased heart performance in diabetic rats. The concentrations of glucose, glycerol, triacylglycerol, cholesterol, and phospholipids in serum were lower compared with untreated diabetic animals. On the other hand, the lipid and the carnitine content of heart and liver increased in the etomoxir-treated rats. Carnitine palmitoyl transferase inhibitors have clear antidiabetic effects, but before using as an oral antidiabetic drug, the long-term changes of the lipid and carnitine metabolism should be evaluated.
Reinauer
H
H
Diabetes-Forschungsinstitut, Heinrich-Heine-Universität Düsseldorf.
Adrian
M
M
Rösen
P
P
Schmitz
F J
FJ
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002621:Chemistry; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D014280:Triglycerides; C035111:B 807-27; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; C054207:etomoxir; D002331:Carnitine