Tryptophan and the control of plasma glucose concentrations in the rat

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Abstract
Injection of L-tryptophan (750 mg/kg body wt) led to pronounced hypoglycemia in fed and 48 h-starved rats. The hypoglycemic effect is blocked by pre-treatment with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-.alpha.-(3,4-dihydroxybenzyl)-.alpha.-hydrazinopropionic acid monohydrate] or methysergide and potentiated by pargyline. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycemia than tryptophan. Other tryptophan metabolites were not associated with hypoglycemia. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. Metabolite concentration changes in the livers from tryptophan-treated 48 h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycemic response. Tryptophan treatment was associated with a significant increase in the plasma [.beta.-hydroxybutyrate]/[acetoacetate]ratio; there were no changes in the plasma concentrations of urea, triacylglycerol, non-esterified fatty acids and glycerol. These observations suggest that the hypoglycemic action of tryptophan is mediated through formation of intracellular 5-hydroxytryptamine, and is unrelated to the inhibition of gluconeogenesis. It is unlikely that this increased synthesis of 5-hydroxytryptamine involves directly either the adrenal glands or the CNS.