Subcellular myocardial abnormalities in experimental diabetes: role of long-chain acylcarnitines.
Long-chain acylcarnitines are membrane-active intermediates of fatty acid metabolism whose intracellular accumulation has been implicated in the myocardial injury associated with both streptozotocin-induced diabetes and acute ischemia. In the present study, rats treated with streptozotocin (50 mg/kg i.v.) exhibited increases in myocardial long-chain acylcarnitines comparable to those previously reported to occur in moderate to severe ischemic injury. With the exception of a reduction in the sedimentable (lysosome-associated) fraction of myocardial N-acetyl-beta-glucosaminidase and a decrease in sarcoplasmic reticulum K+, Ca++-stimulated ATPase activity, other characteristic indices of myocardial ischemic damage, notably inhibition of sarcolemmal and mitochondrial ATPase activities as well as alterations in the ionic composition of myocardial tissue, were not apparent in the hearts of the streptozotocin-diabetic animals. On the basis of in vitro studies using palmitylcarnitine, it does not seem that differential sensitivity to long-chain acylcarnitine inactivation can explain the preferential inhibition of the sarcoplasmic reticulum ATPase enzyme observed in vivo. Our data are consistent with the findings of others suggesting that long-chain acylcarnitines are unlikely to be the most important or sole mediators of myocardial ischemic injury. However, a modulatory role of these substances in myocardial ischemic injury or in determining the increased susceptibility of diabetics to the complications of ischemic heart disease cannot be excluded at present.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D004912:Erythrocytes / Q000032:analysis; D005260:Female; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010172:Palmitoylcarnitine / Q000378:metabolism; D010713:Phosphatidylcholines / Q000097:blood; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013109:Sphingomyelins / Q000097:blood; D013311:Streptozocin
D010713:Phosphatidylcholines; D013109:Sphingomyelins; D010172:Palmitoylcarnitine; D013311:Streptozocin; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium; D002331:Carnitine