Evidence of a peripheral and a central effect of oxytocin on pancreatic hormone release in rats

Evidence of a peripheral and a central effect of oxytocin on pancreatic hormone release in rats
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DOI:
10.1159/000126978
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发表时间:
1996-04-01
期刊:
影响因子:
4.1
通讯作者:
UvnasMoberg, K
UvnasMoberg, K
中科院分区:
医学2区
文献类型:
--
作者:
Bjorkstrand, E;Eriksson, M;UvnasMoberg, K

文献摘要

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本研究的目的是调查如何催产素皮下(SC)和脑室内(ICV)的影响胰岛素,胰高血糖素和葡萄糖的分泌,并调查是否对这些变量的哺乳期大鼠催产素能机制介导的影响。雄性大鼠给予催产素,剂量为2或20 ng(SC)或2或200 ng(ICV)。收集躯干血,通过放射免疫法进行激素分析。皮下注射催产素显著增加胰岛素、胰高血糖素和葡萄糖水平。ICV给予两纳克催产素对胰高血糖素和葡萄糖水平没有影响,但在该时间点引起胰岛素水平显著升高。阿托品可消除这种效应。ICV给药的催产素拮抗剂1-脱氨基-2-D-Tyr-(OEt)-4-Thr-8-Om-oxytocin增加了胰岛素水平本身,因此对催产素诱导的胰岛素分泌的影响难以评估。脑室注射200 ng催产素不仅引起胰岛素,而且还引起胰高血糖素和葡萄糖水平的显着上升。由于该剂量的催产素也引起循环催产素水平的大幅上升,因此这些对葡萄糖和胰高血糖素的影响可能已经在外周部位发挥作用。哺乳期大鼠的葡萄糖和胰高血糖素水平显着增加。这些影响被完全取消预处理催产素拮抗剂。总之,催产素似乎通过两种不同的机制影响胰腺激素分泌。催产素的循环水平升高-例如,如在哺乳大鼠中响应于吮吸所见-伴随胰高血糖素和葡萄糖水平的升高,其被催产素拮抗剂阻断。相反,ICV施用的纳克量的催产素引起胰岛素水平的升高。由于该作用被阿托品阻断,因此可能涉及迷走胆碱能神经元的激活,支配胰腺β细胞。
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-Om-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 beta-cells.