Effect of succinic and malic acids and fructose on ketosis in alloxan-diabetic rats.

The current concept of fatty acid metabolism involves the formation of acetyl CoAl and the condensation of acetyl CoA with oxalacetate upon entrance into the tricarboxylic acid cycle. Therefore, a sufficient amount of oxalacetic acid is necessary for the complete oxidation of fatty acids via the tricarboxylic acid cycle, and, if sufficient oxalacetic acid is not present., ketosis results. Previously (1) we have demonstrated that the administration of various precursors of oxalacetic acid, such as succinic and malic acids, and oxalacetic acid itself, decreases total urinary ketone body excretion in non-diabetic rats made ketotic by the administration of butyric acid. This raises the question as to whether or not these substances would have the same effect in an insulin-deficient preparation. Glucose requires insulin to produce oxalacetate at ti normal rate, but the effect of insulin on the rate of production of oxalacetate from other precursors is unknown, although recent work (2) indicates that insulin is involved in metabolism at the level of the tricarboxylic acid cycle. There are a few reports in the literature on the effects of succinic acid on ketosis in diabetic humans (3), but the results are conflicting. Therefore, we have investigated the effects of succinic and malic acids on ketosis in insulin-deficient rats. In view of the reports that the utilization of fructose is independent of insulin (4), the effects of fructose on ketosis in these diabetic animals were also investigated.