Metergoline, naloxone, and sodium valproate did not modify arginine vasopressin response to insulin-induced hypoglycemia in man

Abstract

The present study was carried out in order to determine whether insulin-induced hypoglycemia exerts its stimulatory effect on plasma concentrations of arginine vasopressin (AVP) by interacting with a serotonergic, a GABA-ergic or an opioid pathway. For this purpose, the effect of the serotonergic antagonist metergoline (10 mg/day for 4 days po), the GABA-ergic agonist sodium valproate (600 mg in three divided doses po) and the opioid-receptor blocker naloxone (10 mg in a iv bolus) on the AVP response during an insulin (0.15 IU/kg bw) tolerance test (ITT) was evaluated in three groups of 6 normal men each. In all men, control ITTs were performed without drug treatments. Basal and ITT-stimulated AVP secretion was not modified by drug administration, suggesting that serotonergic, GABAergic and naloxone-sensitive opioid receptors are not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.

Effects of the Gabaergic Agent Sodium Valproate on the Arginine Vasopressin Responses to Hypertonic Stimulation and Upright Posture in Man

“…While our previous studies did not show a GABAergic involvement in the AVP response to insulin-induced hypoglycaemia in man (Chiodera et al, 1988), the results of the present study provide evidence that in man GABAergic stimulation reduces the AVP response to hypovolaemic and hyperosmotic stimuli. From the ability of sodium valproate to antagonize the effects of osmotic and volumetric AVP-releasing stimuli one cannot establish the exact site of the GABAergic inhibition, since the drug freely crosses the blood-brain barrier (Elias et al, 1982;Racagni et al, 1982).…”

“…Studies carried out in rats have shown the presence of a GABAergic innervation of vasopressin secreting neurons in vitro (Sakai et al, 1974;Van den Pol, 1985) and an inhibitory influence of GABA on the vasopressin response to pressure volumetric (Knepel et al, 1980) and osmotic stimuli in vivo (Iovino et al, 1980). On the other hand, in humans, studies of the arginine vasopressin (AVP) response to insulin-induced hypoglycaemia failed to provide evidence of a GABAergic involvement (Chiodera et al, 1988). We wondered whether differences between man and rat could be attributed to different regulation in the AVP response to different stimuli or might represent a substantial difference between species in the neuroendocrine control of AVP secretion.…”

Different Effects of the GABAergic Agent Sodium Valproate on the Oxytocin Responses to Angiotensin II and Insulin-Induced Hypoglycemia in Normal Men

“…but not of hypoglycemia-stimu lated OT release, indicating that different neuroendo crine mechanisms control the OT responses to these stimuli. Similar findings have been reported for AVP, which is under GABAergic control when it is stimulated by ANG II [10], but not when it is released in response to insulin-induced hypoglycemia [30], Fischer et al [12] observed strong similarities in the OT and AVP re sponses to hypoglycemia. Our studies show that both hypoglycemia-and ANG-II-stimulated AVP and OT re sponses are equimolar and follow a similar pattern.…”

Influence of residual C‐peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin‐dependent diabetes

“…Concerning stimulatory neurotransmission for AVP, it seems to be cholinergic in the case of stimulation with MCP [23] and adrenergic in the case of hypoglycaemia [24]. Both cholinergic and adrenergic neurotransmission have shown alterations at the hypothalamic-pituitary level in diabetes mellitus [25-281. On the other hand, opioids and/or GABA are classic modulators of AVP secretion in various experimental conditions [29-331; however, neither endogenous opioids nor GABA exert inhibitory effects on the AVP response to hypoglycaemia [34]. Further studies are needed to clarify the mechanism of the neuroendocrine alteration affecting AVP secretion in diabetes mellitus.…”