Pharmacological Doses of Oxytocin Affect Plasma Hormone Levels Modulating Glucose Homeostasis in Normal Man

Abstract

Phramcological doses of oxytocin administered in basal conditions evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin and adrenaline levels. The effects of oxytocin on plasma glucagon and adrenaline levels were potentiated by hypoglycemia. When the endogenous pancreas secretion was suppressed by cyclic somatostatin (150 µg/h) and exogenous glucagon (3.5 µg/h) and insulin (0.2 mU/kg·min) were both replaced, oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels suppressing the glucose infusion rate (GIR) in the first 60 min. On the contrary at higher insulin infusion rate (0.6 mU/kg · min) plasma glucose levels and GIR remained unaffected throughout the study. Oxytocin seems also to potentiate glucose-induced insulin secretion as evidenced by hyperglycemic glucose clamp. In conclusion, pharmacological doses of oxytocin seem to exert a prevalent hyperglycemic effect by a combined action at the liver site (as glycogenolytic agent) and at the endocrine pancreas (as a stimulatory agent of A cell secretion).

Effects of Oxytocin Delivery on Counter-Regulatory Hormone Response in Insulin-Dependent (Type 1) Diabetic Subjects

“…These latter data were also confirmed in rabbits by Knudtson [13], In normal man, Chiodera et al [14] showed a poten tiating effect of oxytocin only on glucose-induced insulin secretion, while Geenen et al [ 15] failed to evidence any effect of graded oxytocin infusion on carbohydrate me tabolism. Previous studies performed in normal man [5,6] by our group evidenced oxytocin, infused in the same dose range as in the present investigation, to signifi cantly increase basal as well as arginine-induced plasma glucagon levels and to potentiate the A cell response to an insulin-induced hypoglycaemia.…”

“…In previous studies [5,6] performed in normal man, we demonstrated that oxytocin raised plasma glucagon levels in basal conditions, during an insulin-induced hypoglycaemia and after an arginine infusion. This latter finding was also confirmed in diabetic subjects [6].…”

“…Furthermore, the reduction in plasma glucose fall, consequent upon the contemporary infusion of insulin and neuro-hypophysial hormone versus insulin alone, might also be related to the glycogenolytic action of oxy tocin at the liver site, as demonstrated in vitro by Hens et al [16] and in normal man by ourselves [5], These data appear to us very important, especially in the light of the results provided in long-standing insulindependent diabetic subjects with blunted counter-regula tory hormone reponse as a consequence of autonomic neuropathy [17], In this group of patients many evi dences indicate that glucagon, by its stimulatory effect on glucose production, is the key hormone responsible for the recovery from hypoglycaemia [17][18][19][20]; neverthe less epinephrine, not normally critical, became impor tant when glucagon was deficient [18]. So the utilization of pharmacological doses of oxytocin, intravenously ad ministrated, might be a useful tool for the recovery from hypoglycaemia.…”

The effects of oxytocin on eating behaviour and metabolism in humans

“…In a small study of men, 6 IU (an initial dose of 2 IU plus an infusion of 4 IU over 1 h), but not 3 IU (an initial dose of 1 IU plus an infusion of 2 IU over 1 h) oxytocin intravenously increased insulin levels in response to intravenous administration of glucose (0.33 g/kg) without affecting glucose levels or the glucagon, growth hormone or cortisol responses 110 . Another study reported that continuous intravenous infusion of oxytocin (0.2 IU/min over 60 min) resulted in hyperglycaemia, accompanied by increased release of glucagon, insulin and adrenaline and reduced release of cortisol in healthy, young men aged 21-26 yrs 111 . Furthermore, in response to insulin-induced hypoglycaemia, oxytocin infused intravenously at this dose attenuated the drop in levels of glucose, increased levels of glucagon and adrenaline and reduced cortisol levels 111,112 .…”

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

“…On the other hand, a role of OT in the maintenance and restoration of blood volume and arterial blood pressure has been demonstrated in rats and dogs [18][19][20][21], In light of this observation, stimula tion of OT release by ANG II might be supposed to con tribute to the general pressor effect of ANG II. Concern ing the meaning of the OT response to hypoglycemia, a contribution by OT to glucose homeostasis has been sup posed because of the hyperglycemic effects of OT [22,23], Even though these actions are present at concentra tions higher than those observed in response to insulininduced hypoglycemia in normal subjects, OT is sup posed to play a pathophysiological role in diabetic pa tients [24],…”