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 mamm als. Insulin secretion is regulated by a coordinated interplay of seve ral factors. The role of the indoleamines in the central of insulin se cretion has not been fully elucidated yet. The present study was addre ssed to investigate the function of melatonin and serotonin in the dir ect control of insulin secretion from the pancreatic islets. Explanted rat Langerhans' islets were Created with melatonin or serotonin while also being exposed to specific (glucose) or non-specific (KCl) stimul us either in a pulsatile or long-term manner in a perifusion system. I nsulin content from the effluent tissue culture media was analyzed wit h RIA. Pulsatile administration of melatonin and serotonin alone did n ot alter the basal insulin secretion from the explanted islets even at pharmacological (5 mu M) level. However, insulin response to specific (glucose) or non-specific (KCl) stimulus was significantly reduced wh ile the islets were treated with melatonin (3 to 12 hr, 10 nM to 5 mu M). This effect was reversible and repeatable. Both the start and end of the effect was rapid, evolving and disappearing within 10 min. On t he other hand, under similar experimental protocol, serotonin (at 5 mu M concentration) significantly enhanced both glucose and KCl stimulat ed insulin release. Since the effect of the nonspecific stimulation (w ith KCl) was also altered, melatonin and serotonin seem to alter not o nly the release but also the synthesis of the insulin. Our data show t hat melatonin and serotonin have a direct effect on the insulin secret ion from the pancreatic islets.