Influence of melatonin and serotonin on glucose-stimulated insulin release from perifused rat pancreatic islets in vitro.

Insulin plays a key role in the control of glucose homeostasis in mammals. Insulin secretion is regulated by a coordinated interplay of several factors. The role of the indoleamines in the control of insulin secretion has not been fully elucidated yet. The present study was addressed to investigate the function of melatonin and serotonin in the direct control of insulin secretion from the pancreatic islets. Explanted rat Langerhans' islets were treated with melatonin or serotonin while also being exposed to specific (glucose) or non-specific (KCl) stimulus either in a pulsatile or long-term manner in a perifusion system. Insulin content from the effluent tissue culture media was analyzed with RIA. Pulsatile administration of melatonin and serotonin alone did not alter the basal insulin secretion from the explanted islets even at pharmacological (5 microM) level. However, insulin response to specific (glucose) or non-specific (KCl) stimulus was significantly reduced while the islets were treated with melatonin (3 to 12 hr, 10 nM to 5 microM). This effect was reversible and repeatable. Both the start and end of the effect was rapid, evolving and disappearing within 10 min. On the other hand, under similar experimental protocol, serotonin (at 5 microM concentration) significantly enhanced both glucose and KCl stimulated insulin release. Since the effect of the non-specific stimulation (with KCl) was also altered, melatonin and serotonin seem to alter not only the release but also the synthesis of the insulin. Our data show that melatonin and serotonin have a direct effect on the insulin secretion from the pancreatic islets.