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.

Bromocriptine Reduces Obesity, Glucose Intolerance and Extracellular Monoamine Metabolite Levels in the Ventromedial Hypothalamus of Syrian Hamsters

“…Hyperinsulinemia, in turn, may complete a positive feedback loop by increasing sympathetic activity [45, 46] and plasma tryptophan [47] and thus, increasing central serotonin levels [48, 49, 50, 51]. Moreover, decreases in plasma insulin induced by streptozotocin in rats are associated with decreases in brain tryptophan levels, serotonin synthesis and turnover, and NE turnover which are all restored to normal with insulin replacement therapy [52, 53, 54].…”

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…Furthermore, STZ-treated rats have increased plasma BCAA concentrations, plus low levels of tryptophan and diminished serotonin production in the brain [69,71]. Insulin treatment increases brain levels of tryptophan, and thereby the substrate for serotonin production, in these animals [71,77].…”

Depression Can Beget Obesity Can Beget Depression

“…Although the increase may be limited to [15][16][17][18][19][20] pounds, this weight gain may be sufficient to change the individual's classification from overweight to obese. The mood stabilizers and antipsychotic agents can promote weight gain both by suppressing satiety and by diminishing physical activity 8 ; these effects are especially troublesome for patients who are receiving several medications, each with its own potential for increasing body weight.…”

“…(Diabetes similarly reduces brain tryptophan and serotonin in rats. 18 ) Attempts to treat obesity by decreasing carbohydrate intake (as with the high-protein Atkins Diet or South Beach Diet) only exacerbate the reduction in brain serotonin, often leading to carbohydrate craving, deterioration of mood (anger, depression), and insomnia. 19 Paradoxically, the consumption of dietary proteins-all of which, unlike carbohydrates, contain tryptophan-fails to elevate and may actually reduce brain tryptophan levels and serotonin synthesis.…”