The significance of tryptaminergic mechanisms in relation to insulin secretion was studied in mice by measuring the serum insulin and the in vitro release of insulin under various conditions shown to influence the β-cell level of 5-hydroxytryptamine. Depletion of monoamines by reserpinization led to elevated serum insulin levels. However, microdissected islets from lean mice treated with reserpine released less insulin in response to glucose than islets taken from untreated controls. Combined in vivo treatment with 5-hydroxytryptophan and the monoamine oxidase inhibitor nialamide did not affect the serum insulin level but completely abolished the glucose-stimulated insulin release from the microdissected islets. Histochemical studies of free islet cells revealed that 5-hydroxytryptophan could be accumulated and decarboxylated in islets microdissected from obese-hyperglycemic mice. The insulin release from isolated islets appeared to be somewhat enhanced at a low glucose level during and after preincubation with 5-hydroxytryptophan. No glucose-stimulation was recorded for islets preincubated with 5-hydroxytryptophan. The 5-hydroxytryptamine inhibitor 2-brom-d-lysergic acid diethylamide did not affect insulin release in vitro. It is suggested that elevated β-cell levels of endogenously formed 5-hydroxytryptamine inhibit the glucose-stimulated insulin release in mice.
Endogenous 5-Hydroxytryptamine - 5-Hydroxytryptophan - Monoamine Oxidase Inhibitor - Reserpine - Serum Insulin - Insulin Release In Vitro - Microdissected Islets - Mice
