Dihydroergotamine, but not naloxone, counteracts lithium as an inhibitor of glucose-induced insulin release in isolated rat islets in vitro.

Lithium exerts an inhibitory effect on glucose-induced insulin release. Lithium (5 mmol/l) added 30 min prior to glucose stimulation or together with glucose (16.7 mmol/l) failed to affect first phase, but reduced second phase glucose-induced insulin release by 35%. Similar results were obtained when islets isolated from rats following long-term oral lithium treatment were perifused with glucose (16.7 mmol/l). The inhibitory effect of lithium was counteracted by pretreatment of the rats with the alpha-adrenergic blocking agent dihydroergotamine, whereas the opiate antagonist naloxone had no apparent effect on lithium-induced inhibition of glucose-stimulated insulin release.