Acetoacetate as fuel of respiration in the perfused rat heart

Abstract

Removal of acetoacetate and glucose, the formation of [beta]-hydroxybutyrate and lactate, the consumption of oxygen and the changes in the concentrations of glycogen were measured in the perfused heart preparation described by Bleehen and Fisher (1954). Acetoacetate, [beta]-hydroxybutyrate, glucose and insulin, alone and in combinations, were added to the perfusate. Acetoacetate was rapidly removed from the perfusate. At concentrations above 4 mM about half was recovered as [beta]-hydroxybutyrate. At low concentrations (below 0.25M) acetoacetate also disappeared rapidly but little was reduced to [beta]-hydroxybutyrate. No intermediates of oxidation accumulated and the acetoacetate not accounted for as [beta]-hydroxybutyrate may therefore be taken to be completely oxidized. Added D(-)-[beta]-hydroxybutyrate was as readily oxidized as acetoacetate. Insulin with or without glucose somewhat lowered the rate of oxidation of acetoacetate. It is calculated from the rates of oxygen consumption and acetoacetate oxidation that in the absence of insulin acetoacetate (5 mM) contributed 73-82% to the fuel of respiration. Insulin decreased this value to 51-64%, in the presence or the absence of glucose. Acetoacetate decreased the oxidation of glucose in the presence or in the absence of insulin. It halved the uptake of glucose by the heart in the presence of insulin. Glucose when added as the sole substrate contributed 24% to respiration and insulin raised this to 57%. When acetoacetate and glucose were added, glucose contributed 4% in the absence, and 15% in the presence, of insulin. The data indicate that acetoacetate is oxidized in preference to glucose and endogenous substrates. Insulin increased the contribution made to respiration by endogenous substrates. This is taken to indicate that insulin has effects other than accelerating the entry of sugars into the tissue.