Facilitating Effect of Insulin on Brain 5-Hydroxytryptamine Metabolism

Abstract

In this study we investigated the effect of insulin on striatal 5-hydroxytryptamine and tryptamine in streptozotocin-diabetic and in normal rats. Streptozotocin-diabetic rats show a reduction in rat striatal tryptophan, 5-hydroxytryptamine, and 5-hydroxyindole acetic acid, an effect observed at 7 or 14 days after the treatment began. In addition, the accumulation of striatal tryptamine in pargyline-treated rats was reduced at 14 days. Insulin administration produced an increase in rat striatal tryptophan concentration that was observed within 2 h following its administration. By 6 h, however, the striatal tryptophan concentrations were significantly reduced. No changes in rat striatal 5-hydroxytryptamine were observed following the insulin administration, but the treatment induced significant increases in 5-hydroxyindole acetic acid that were observed at 2, 3, 4, and 6 h after insulin administration. The administration of insulin to diabetic rats had a tendency to reverse the decreases in 5-hydroxytryptamine metabolism observed in these animals. Treatment with tryptophan (12–25 mg kg^–1) markedly increased rat striatal tryptophan, but did not affect 5-hydroxytryptamine metabolism, an effect that was only observed after the administration of higher doses (50–100 mg kg^–1). This is in contrast to the effect of insulin that produces a lesser increase in striatal tryptophan accompanied by an increase in 5-hydroxytryptamine metabolism, indicating that in addition to the inrease in tryptophan availability that it produces, it also possesses some other facilitatory effect on 5-hydroxytryptamine metabolism.

Changes in Brain Monoaminergic Neurotransmitter Concentrations in Rat after Intracerebroventricular Injection of Streptozotocin

“…Th� most fre quent result reported has been a reduction in the cerebral tissue concentration of the 5-HT precursor tryptophan by 30--50% observed 1-4 weeks after intraperitoneal injection of STZ (Curzon and Fernando, 1977;Mackenzie and Trulson, 1978a;Trulson et aI., 1986). In contrast to these reports, according to which there were no alterations in the brain tissue levels of 5-HT or 5-HIAA, concentra tions of these were also reduced 2 weeks after in traperitoneal STZ treatment in the study of Kwok and Juorio (1987). In addition, a diminished synthe sis and turnover rate of cerebral 5-HT were found in rats with STZ-induced diabetes 2-3 weeks (Crandall et aI., 1981) and 4-6 weeks (Trulson et aI., 1986) after the injection.…”

Cognitive Function in an Elderly Population With Persistent Impaired Glucose Tolerance

“…On the other hand, insulin has access to the brain, where it may act as a neuromodulator (32). Insulin has been shown to reduce cholinergic activity in cultured striatal neurons (33) and to accelerate the turnover of monoamines in the brain (34,35). Therefore, in hyperinsulinemic subjects, altered cholinergic and/or monoaminergic activity could account for cognitive impairment.…”

Effects of an Oral Glucose Load on Plasma Neurotransmitters in Humans: Involvement of REM Sleep?

“…Al though insulin also stimulates the central 5HT system [3], the physiological connections between central and EC cell-circulating 5HT systems have not been established. However, recent findings have demonstrated that medul lar vagal nuclei receive strong excitatory input arising front central 5HT nuclei [14.…”

“…Insulin likewise activates central serotonerIt is a known fact that the administration of either glu-gic and parasympathetic systems [3,4], Nonetheless, how cose or insulin increases plasma noradrenaline (NA) in these centrally induced effects reflect on plasma neuro normal humans. This effect is secondary to the stimula-transmitter levels is still unknown.…”