Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate-pyruvate and l-glycerol 3-phosphate-dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles

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Abstract
The rate of oxidation of pyruvate in rat hearts or diaphragms perfused or incubated in vitro with buffer alone or buffer containing either pyruvate or glucose and insulin was measured, and the effects of alloxan-diabetes and starvation and of the addition of fatty acids or ketone bodies in vitro investigated. In rat heart perfused with medium containing pyruvate the oxidation of unlabelled or of [C14] -pyruvate was inhibited (by approx. 70%) by n-octanoate, butyrate, palmitate, acetoacetate and DL-[beta]-hydroxybutyrate and by alloxan-diabetes. The oxidation of pyruvate formed inthe muscle from breakdown of glycogen was inhibited by [beta]-hydroxybutyrate and palmitate. In hearts perfused with medium containing glucose and insulin the oxidation of pyruvate formed from glucose was inhibited by octanoate, butyrate and palmitate and by alloxan-diabetes. In rat hemidiaphragms incubated in medium containing pyruvate the oxidation of unlabelled or [C14]pyruvate was inhibited by butyrate and palmitate and by diabetes and starvation. These agents also inhibited the oxidation of pyruvate formed from glucose. In rat hearts or rat hemidiaphragms perfused or incubated in vitro with medium lacking glucose, the addition of pyruvate to the perfusion medium did not significantly impede the breakdown of glycogen. In rat heart and rat hemidiaphragms the lactate/pyruvate ratio in the perfusion or incubation medium was increased by glucose, anoxia, salicylate, fatty acids and ketone bodies, and decreased by albumin, alloxan-diabetes and starvation (for 48 hr.). The glycerol phosphate/dihydroxyacetone phosphate ratio in the muscles was increased by butyrate and decreased by diabetes and starvation. It is concluded: that the oxidation of pyruvate in rat heart and rat diaphragm muscles may be inhibited in diabetes because of the greater availability of fatty acids and ketone bodies for respiration in this condition; that glycolysis in these muscles is not reversible to any significant extent; that the NADH2/NAD ratio in cell sap is increased by glucose, anoxia, salicylate, fatty acids and ketone bodies, and diminished in alloxan-diabetes and starvation. The possibility that the inhibitory effects of diabetes, fatty acids and ketone bodies on pyruvate oxidation are due to inhibition of pyruvate dehydrogenase by a rise in the acetyl-CoA/CoA ratio is discussed.