Lithium Ions and Insulin: Effects on Carbohydrate and Electrolyte Metabolism

It is not yet possible to interpret thesc results completely. The acids affected are all dicarboxylic acids with a chain length of between C, and Cs. The glutarate derivatives showed the greatest increases. Citrate excretion was unchanged (Bond et d., 1972). This suggests that the range of compounds affected is determined by chemical structure rather than metabolic relationship, and that this is a transport effect. On the other hand several of the acids are intermediates in the tricarboxylic acid cycle, and in a preliminary experiment the increased excretion of tricarboxylic acid-cycle intermediates produced by intravenous infusion of succinate (Nordmann et at., 1955) was accompanied also by an increased excretion of glutarate. Thus i t is possible that the effect of lithium salts is primarily on the tricarboxylic acid cycle, and that the other metabolites are excreted in unusual quantities because of competition for a common transport system. Berl & Clarke (1971) have reported that with guinea-pig brain slices lithium salts greatly affect the pattern of incorporation of [ l-14C]acetate into amino acids derived from the tricarboxylic acid cycle. This suggests that the effect of lithium salts on these intermediates may not be restricted to the kidney and may have some relevance to its therapeutic effect.