Inhibition of insulin secretion by serotonin and dopamine: Species variation

Serotonin and dopamine are potent inhibitors of insulin secretion in the in vitro golden hamster pancreas system. In the present studies, the effects of serotonin and dopamine on insulin secretion in several species were investigated. In vivo glucose-stimulated insulin release was inhibited in white rabbits by constant infusion of serotonin (25 ʼg/min), and in white mice by an intravenous bolus of serotonin (0.25 mg). Whereas 5 × 10^-5M serotonin inhibited glucosemediated insulin release from golden hamster pancreas in vitro, 2 × 10^-3M serotonin was required to inhibit insulin release from pieces of rabbit or mouse pancreas. In contrast, all three species had a similar in vitro sensitivity to the inhibition of insulin secretion by dopamine. Histochemical studies have shown that adrenergic nerves of golden hamster islets contain large amounts of norepinephrine, but none is visible in islets of albino rabbits and mice. To determine if the increased susceptibility of the hamster pancreas to inhibition of insulin secretion by serotonin was related to its high content of norepinephrine, pancreas from hamsters depleted of catecholamines by reserpine was studied. This pre-treatment led to a marked decrease in sensitivity to serotonin inhibition of insulin secretion but no alteration in sensitivity to exogenous norepinephrine. These findings suggest that: 1) serotonin and dopamine inhibit insulin release in all species studied; and 2) serotonin inhibition of insulin secretion in golden hamster pancreas is partially dependent upon the release of endogenous norepinephrine from adrenergic nerves in the islets of Langerhans.