Intermediary Metabolism in Diabetes Mellitus on the Synthesis of Carbohydrate from Fat in the Liver and from Acetoacetate in the Kidney* by William C. Stadie,

The possible conversion of fatty acids into carbohydrates by mammalian tissues continues to be a controversial subject. Because carbohydrates are convertible into fats, and fats, in certain forms of plant life, are unquestionably converted into carbohydrates, the non-reversibility of this reaction in animal tissues is accepted with reluctance. Moreover, this conversion is the pivotal reaction in the overproduction hypothesis of diabetes mellitus according to which the main effect of insulin is the inhibition in the liver of the reaction, fatty acids + oxygen = carbohydrates. Evidence concerning the possible intermediary pathways of fatty acids to carbohydrates is meager. The ‘2-, 4-, or 6-carbon oxidation products of fatty acids enumerated in Table I are conceivable precursors of carbohydrate. The evidence in the literature indicates that all but butyric acid, ketol, succinic acid, and acetoacetic acid can be eliminated from consideration. The first three have never been shown to be intermediaries in hepatic fatty acid catabolism. Acetoacetic acid has been shown definitely not to be a precursor of carbohydrate when perfused through the liver. Therefore since it is generally accepted that the liver is the sole site of new carbohydrate formation, the evidence for a possible pathway of fatty acid to carbohydrate is essentially nil.