Tryptophan and the control of plasma glucose concentrations in the rat.
1. Injection of L-tryptophan (750 mg/kg body wt.) led to pronounced hypoglycaemia in fed and 48 h-starved rats. 2. The hypoglycaemic effect is blocked by pretreament with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrate] or methysergide, and potentiated by pargyline. 3. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycaemia than does tryptophan. Other tryptophan metabolites were not associated with hypoglycaemia. 4. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycaemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. 5. Metabolite concentration changes in the livers from tryptophan-treated 48h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycaemic response. 6. 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, triacyglycerol, non-esterified fatty acids and glycerol. 7. These observations suggest that the hypoglycaemic 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 central nervous system.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D007003:Hypoglycemia / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D014364:Tryptophan; D010293:Pargyline; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D008784:Methysergide