Endogenous opioids modulate the oxytocin response to insulin-induced hypoglycaemia and partially mediate the inhibitory effect of ethanol in man.
Abstract The possible inhibition exerted by ethanol on the oxytocin (OT) response to insulin-induced hypoglycaemia was tested in man. Furthermore, the possibilities that endogenous opioids play a role in the control of hypoglycaemia and/or ethanol action on OT were examined. Insulin tolerance tests were performed in three groups of eight age- and weight-matched normal men treated with: 1) naloxone, group 1 1 mg bolus naloxone + 2.5 mg over 105 min, group 2 2 mg bolus naloxone + 5 mg over 105 min, group 3 4 mg bolus naloxone + 10 mg over 105 min; 2) ethanol (50 ml in 110ml of whiskey) to all the groups; 3) a combination of ethanol + naloxone; 4) normal saline. Furthermore, the effect of ethanol + naloxone (4+10mg) in the absence of insulin-induced hypoglycaemia was evaluated in seven additional subjects. During this latter test, the plasma levels of OT remained unchanged. Insulin-induced hypoglycaemia produced a 2.2-fold increment in plasma OT levels in the control experiments. This response was not changed by the treatment with the lowest dose of naloxone (1+2.5mg) in group 1, but it was significantly enhanced by administration of naloxone at higher doses (mean peak OT levels rose 2.8-fold in both group 2 and group 3). In all subjects the OT response to hypoglycaemia was completely abolished by ethanol. However, when ethanol was given together with naloxone, the hypoglycaemia-induced OT rise was only partially inhibited by ethanol. At all doses naloxone produced similar effects; in fact, in all groups OT rose 1.5-fold in response to hypoglycaemia during insulin tolerance test + ethanol + naloxone. Neither naloxone nor ethanol altered the basal secretion of OT, as tested during 45 min before the insulin tolerance test. These data demonstrate that the OT response to insulin-induced hypoglycaemia is inhibited by ethanol. Furthermore, the data indicate that endogenous opioids are involved in the control of hypoglycaemia-stimulated OT secretion and partially modulate ethanol inhibitory action.
Coiro
V
V
Divisions of Internal Medicine and University of Parma, Parma, Italy.
Capretti
L
L
Davoli
C
C
Speronij
G
G
Bianconi
L
L
Cavazzini
U
U
Marcato
A
A
Papadia
C
C
Volpi
R
R
Chioderat
P
P