Substrate utilization by myocardium and skeletal muscle in alloxan-diabetic dogs.

WIENER, ROSLYN, AND JOHN J. SPITZER. Substrate utilization by myocardium and skeletal muscle in atloxan-diabetic dogs. Am. J. Physiol. 225(6) : 1288-l 294. 1973.-Myocardial and skeletal muscle substrate utilization was investigated in eight alloxan-diabetic dogs. A continuous infusion of palmitate1 -14C was administered throughout the experiments. At control plasma free fatty acid (FFA) concentrations of 0.75 ,umole/ml and ketone body levels of 1 pmole/ ml, FFA oxidation accounted for about 50% of the measured CO2 production by both tissues. Endogenously produced acetoacetate (&AC) and P-hydroxybutyrate (POHB) were removed by both tissues (AcAc preferentially), and the total ketone uptake, if completely oxidized, would have accounted for about 4Oa/, of the COZ production. Upon elevation of arterial ketones to 4 pmoles/ml by constant infusion of Na-DL-POHB, arterial FFA concentration and turnover decreased by about 3070. There was a 60% decrease in FFA oxidation by both tissues, with a commensurate decrease in CO2 production attributable to FFA oxidation. Ketone body uptake by both tissues during POHB infusion could have provided major metabolic support in the absence of consistent lactate or glucose uptake. The respiratory quotient of both tissues rose during POHB infusion. These studies indicate that, at sufficiently high arterial levels, ketone bodies may replace FFA as the major fuel of both myocardium and skeletal muscle in the diabetic dog.