Studies with (+)—Octanoylcarnitine in Experimental Diabetic Ketoacidosis

Abstract

The ability of (+)-decanoylcarnitine to inhibit ketogenesis in perfused livers from severely ketotic alloxan diabetic rats and to cause the rapid reversal of ketoacidosis in intact animals was shown not to be the result of a detergent action of this compound, since no such effects were seen when similar experiments were carried out with (−)-decanoylcarnitine. Comparison of the hexanoyl, octanoyl and decanoyl esters of (+)-carnitine for their antiketogenic capacity in perfused Hvers from alloxan diabetic rats revealed that the eight- and ten-carbon homologues were equally effective, with the six-carbon species having less inhibitory properties. When tested in vivo, both in the presence and absence of insulin, the eight-carbon species exhibited the greatest hypoketoiemic potential. Further studies with (+)-octanoyIcarnitine showed that (a) its potent effects in the rat are completely reversible; (b) it is not metabolized in this animal species and is rapidly excreted by the kidneys; (c) it has a far lower hemolytic capacity than (+)-decanoylcarnitine; and (d) it is capable of reversing severe ketoacidosis when administered orally, although the doses required using this procedure are much greater than those needed when the agent is given intravenously. It is concluded that (+)-acylcarnitines are useful tools for studies of metabolic regulation both in vitro and in vivo. In this regard the compound of choice would seem to be (+)-octanoylcarnitine.