Opioid-mediated inhibition of oxytocin during insulin-induced hypoglycemic stimulation of vasopressin in man.
We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulin-induced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P less than 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Saline-infused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 +/- 0.4 pmol/l before insulin to 3.2 +/- 1.3 pmol/l at 45 min (P less than 0.05). We conclude that there is opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.
Seckl
J R
JR
Department of Medicine, Charing Cross and Westminster Medical School, Westminster Hospital, London, UK.
Haddock
J A
JA
Dunne
M J
MJ
Lightman
S L
SL
D000328:Adult; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects*
D007328:Insulin; D011957:Receptors, Opioid; D001127:Arginine Vasopressin; D009270:Naloxone; D010121:Oxytocin