Serotonin Enhances Beta-Endorphin Secretion to Lower Plasma Glucose in Streptozotocin-Induced Diabetic Rats

Although serotonin, serotonin uptake inhibitors and serotonin precursors (including tryptophan or 5- hydroxytryptophan) are known to have hypoglycemic action in rodents or human, it is not clear whether serotonin has hypoglycemic effect in streptozotocin-induced diabetic rats( STZ- diabetic rats). The aim of this study was to investigate the action of serotonin in regulating the plasma glucose STZ-diabetic rats. Plasma glucose, insulin, beta- endorphin and adrenaline were assessed after intraperitoneal administration of serotonin. Serotonin produced hypoglycemic effects without altering plasma insulin and adrenaline levels but increasing beta-endorphin level in STZ-diabetic rats. The glycogen content in soleus muscle was increased at 90 min after application of serotonin (0.3 mg/ kg) in STZ- diabetic rats. Dihydroergotamine (non- selective 5-HT receptor blocker) and pimozide (5-HT7 receptor blocker) abolished the hypoglycemic effect of serotonin in STZ- diabetic rats. Serotonin-induced hypoglycemic effect in association with the increase of beta-endorphin release was abolished in bilaterally adrenalectomized STZ- diabetic rats. In isolated adrenal gland of STZ-diabetic rats, the increase of beta-endorphin secretion in response to serotonin was reduced by either dihydroergotamine or pimozide. Pretreatment with naloxone (1.0 mg/kg, i.p.) prevented serotonin-induced plasma glucose lowering effect in STZ-diabetic rats. The results demonstrated that serotonin may activate 5 -HT7 receptor on rat adrenal gland to enhance of beta-endotphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats. (C) 2007 Elsevier Inc. All rights reserved