PRESYNAPTIC SYMPATHETIC MECHANISM IN THE INSULINOSTATIC EFFECT OF EPINEPHRINE IN MOUSE PANCREATIC-ISLETS

The catecholamines inhibit insulin release. It is not established whet her presynaptic mechanisms contribute to this effect. We therefore exa mined the relative contribution of presynaptic and postsynaptic mechan isms to the insulinostatic effects of epinephrine and norepinephrine. Mice were injected with B-hydroxydopamine (6-OHDA; 0.19 mmol/kg) or it s vehicle. Islets were isolated after 48 h. Islets from vehicle-inject ed control animals contained numerous tyrosine hydroxylase (TH)-immuno reactive nerve terminals (marker for sympathetic nerves). In contrast, TH-immunoreactive nerves were not detected in islets from 6-OHDA-trea ted animals, indicating sympathetic denervation. Basal (5.6 mmol/l glu cose) or glucose-stimulated (16.7 mmol/l) insulin secretion did not di ffer between incubated islets from vehicle-injected control animals an d islets from 6-OHDA-treated animals. The insulinostatic effect of epi nephrine, but not that of norepinephrine, was markedly impaired in isl ets from 6-OHDA-treated animals: the lowest effective insulinostatic c oncentration of epinephrine was 0.01 nmol/l in islets from vehicle-inj ected animals and 1 nmol/l in islets from 6-OHDA-treated animals. We c onclude that in isolated mouse islets the insulinostatic effect of epi nephrine, but not that of norepinephrine, partially depends on sympath etic nerve terminals, suggesting an important role for presynaptic mec hanisms in epinephrine-induced inhibition of insulin secretion.