THE EFFECT OF INSULIN UPON THE KETONE METABOLISM OF NORMAL AND DIABETIC CATS

Abstract

Insulin Effect on Ketone Metabolism Kahn (1937) performed similar experiments and came to the same conclusion.Barnes, MacKay, Moe, and Visscher (1938) demonstrated a disappearance of P-hydroxybutyrate from heart-lung preparations of normal dogs and goats.Recently Blixenkrone-Moller (1938, a, b) showed in a convincing manner, by perfusion experiments on the hind limbs of normal and diabetic cats, that t'here was an active utilization of ketones by muscle.This was markedly increased in the contracting muscle, and Blixenkrone-Mgller (1938, b) concluded that ketone oxidation might furnish a considerable fraction of the total energy requirements.Toeniessen and Brinkman (1938), from similar perfusion experiments in the normal rabbit, also concluded that ketone bodies formed in the liver are burned in the muscles.Hypothesis of Multiple Alternate Oxidation of Fatty Acids-As early as 1916, Hurtley rejected the Knoop hypothesis of successive p oxidation as an explanation of the mechanism of production of ketones in the diabetic.Large amounts of the intermediate fatty acids (butyric, caproic, etc.) should be formed in a diabetic excreting 70 gm. of ketones a day.But Hurtley found no significant amounts of butyric acid in the blood or tissues in such a case.He therefore proposed the hypothesis that the fatty acid is attacked at alternate carbon atoms simultaneously along the whole length of the carbon chain according to the scheme, . ..CHz.CH2.CHZ.CHZ.CHZ.CHZ. . .= . ..CO.CH~.CO.CH~.CO.CHZ.. .Jowett and Quastel (1935) studied the rate of formation of ketones from fatty acids by liver slices.They also abandoned the successive ,8 oxidation hypothesis and adopted that of Hurtley, which they called the "multiple alternate oxidation" hypothesis.According to it, the fatty acids undergo an oxidation throughout the entire fatty chain, alternate carbon atoms being affected.As a result, the entire molecule breaks down into acetoacetic acid and perhaps other acid products.Deuel, Hallman, But&, and Murray (1936) studied the rate of excretion of ketone bodies in rats after feeding ethyl esters of fatty acids.Their results indicated that in the case of palmitic, stearic, and oleic acids at least 3 molecules of ketones were formed per molecule of fatty acid oxidized, and they therefore supported the hypothesis of multiple alternate oxidation.Blixenkrone-M@ller (1938, a) compared the oxygen consumption