Acute changes in brain tryptophan and serotonin after carbohydrate or protein ingestion by diabetic rats.

Abstract

In normal, fasting rats, intubation with glucose did not alter serum tryptophan, but it did reduce serum concentrations of the large neutral amino acids, tryptophan's competitors for brain uptake. The serum ratio of tryptophan to the sum of these competitors, which predicts brain tryptophan uptake, was thus increased. Brain tryptophan, serotonin (which is synthesized from tryptophan), and 5-hydroxyindoleacetic acid levels also increased. Such increases in brain serotonin are potentially important, since serotonin is a neurotransmitter. Changes in its level may indicate altered release by neurons and, thus, modified brain function. In contrast, glucose intubation of fasting streptozotocindiabetic rats elicited only a small increase in the serum tryptophan ratio. Brain tryptophan increased slightly; no changes occurred in brain serotonin or in 5-hydroxyindoleacetic acid. Similar effects were noted when fasting diabetic rats consumed a single, carbohydrate meal. However, brain indoles did increase after carbohydrate ingestion in diabetic rats that received an insulin injection at the time food was presented. Effects of ingesting a protein-containing meal were also studied. In normal rats, consumption of this meal increased the serum tryptophan ratio slightly. Brain tryptophan and serotonin levels were unchanged. In diabetic rats, ingestion of the protein-containing meal often lowered the serum tryptophan ratio. Brain tryptophan also fell in diabetic rats when the serum tryptophan ratio was reduced, but brain 5-hydroxyindoles did not fall. The data demonstrate that the absence of a carbohydrate-induced increment in brain indole levels follows indirectly from the absence of the insulin-induced rise in the serum tryptophan ratio. The diabetic rat's inability to experience normal carbohydrate-induced increments in brain serotonin suggests that brain functions, normally dependent on such neurochemical signals, may be abnormal.