Evidence of a Peripheral and a Central Effect of Oxytocin on Pancreatic Hormone Release in Rats

Abstract

The aim of the present study was to investigate how oxytocin given subcutaneously (SC) and intracerebroventricularly (ICV) influences the secretion of insulin, glucagon and glucose and to investigate whether the effect on these variables of suckling in lactating rats is mediated by oxytocinergic mechanisms. Male rats were given oxytocin in doses of 2 or 20 ng (SC) or 2 or 200 ng (ICV). Trunk blood was collected and hormone analysis performed by radioimmunoassay. Subcutaneous injections of oxytocin increased insulin, glucagon and glucose levels significantly. Two nanograms oxytocin given ICV had no effect on glucagon and glucose levels but caused a significant rise in insulin levels at this time point. This effect was abolished by atropine. The oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin administered ICV increased insulin levels itself and therefore the effect on oxytocin-induced insulin secretion was difficult to evaluate. Intracerebroventricular injections of 200 ng oxytocin caused a significant rise not only of insulin but also of glucagon and glucose levels. Since this dose of oxytocin also caused a substantial rise of circulating oxytocin levels, these effects on glucose and glucagon may have been exerted at a peripheral site. Suckling in lactating rats was followed by a significant increase of glucose and glucagon levels. These effects were completely abolished by pretreatment with an oxytocin antagonist. In conclusion, oxytocin seems to influence pancreatic hormone secretion by two different mechanisms. Elevated circulating levels of oxytocin – e.g. as seen in response to suckling in lactating rats – are accompanied by a rise of glucagon and glucose levels which is blocked by the oxytocin antagonist. In contrast, nanogram amounts of oxytocin administered ICV cause a rise of insulin levels. Since this effect was blocked by atropine, it is likely to involve activation of vagal cholinergic neurons, innervating pancreatic β-cells.

Long-Term Changes in Gastrin, Cholecystokinin and Insulin in Response to Oxytocin Treatment

“…In contrast, the decrease in insulin in response to the oxytocin treatment contrasts with the acute effect of oxytocin i.c.v. [3]. Therefore, the long-lasting decrease in insulin in response to the repeated administration of oxytocin might have occurred within the NTS, as suggested by Siaud et al [6].…”

“…The effect, which was abolished by vagotomy and an oxytocin antagonist [6], was supposed to be exerted within the nucleus tractus solitarius (NTS) by activation of inhibitory adrenergic neurons projecting from the NTS to DMX [6, 18, 19]. In contrast, oxytocin has been suggested to stimulate insulin release through the DMX [3, 6]. When oxytocin is administered i.c.v.…”

“…Moreover, the effect on insulin levels of oxytocin i.c.v. was not only blocked by atropine, it was even reversed, since following the atropine injection plasma levels of insulin decreased compared to controls [3, 4, 5]. Thus, oxytocin may have dual opposite effects on insulin release within the DVC, one mediated through the DMX and one through the NTS.…”

“…Oxytocin administered intracerebroventricularly (i.c.v.) has been shown to influence the level of several vagally controlled hormones such as CCK, gastrin and insulin [3, 4, 5]. The effect spectrum caused by oxytocin on the levels of these hormones is complex and both inhibitory as well as stimulatory effects have been demonstrated.…”

“…For example, oxytocin administered i.c.v. has been shown to increase insulin and decrease CCK and gastrin [3, 4], whereas oxytocin administered into the DVC decreases insulin [6]. Since these hormones are under vagal nerve control, it is likely that oxytocin has mediated these effects by changes in vagal nerve activity.…”