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-HT(7) 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-HT(7) receptor on rat adrenal gland to enhance of beta-endorphin secretion, which then stimulates the opioid receptor to increase peripheral glucose utilization, resulting in decreased plasma glucose levels in STZ-diabetic rats.
Chi
Tzong-Cherng
TC
Institute of Pharmacology, College of Medicine, National Taiwan University, No.1, Sec. 1, Jen-Ai Rd., Taipei, Taiwan.
Ho
Yi-Jin
YJ
Chen
Win-Pin
WP
Chi
Tsung-Li
TL
Lee
Shoei-Sheng
SS
Cheng
Juei-Tang
JT
Su
Ming-Jai
MJ
D000311:Adrenal Glands / Q000601:surgery; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004837:Epinephrine / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013311:Streptozocin; D001615:beta-Endorphin / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D009270:Naloxone; D013311:Streptozocin; D001615:beta-Endorphin; D006003:Glycogen; D004837:Epinephrine