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Vasopressin receptors in islets enhance glucose tolerance, pancreatic beta-cell secretory function, proliferation and survival
Biochimie ( IF 3.9 ) Pub Date : 2019-01-21 , DOI: 10.1016/j.biochi.2019.01.008
Shruti Mohan , R. Charlotte Moffett , Keith G. Thomas , Nigel Irwin , Peter R. Flatt

Arginine vasopressin (AVP), a peptide secreted from the posterior pituitary, is chiefly regarded as a hormone involved in the regulation of body fluid balance and osmolality. However, recent evidence has revealed that posterior pituitary hormones can exert important actions on endocrine pancreatic function. In the present study, the presence of AVP receptors, namely Avpr1a (V1a), Avpr1b (V1b) and Avpr2 (V2) was demonstrated in murine islets as well as rodent BRIN BD11 and human 1.1B4 beta-cells. Further to this, AVP was shown to induce significant concentration-dependent (10−12 – 10−6 M) increases of insulin release from both rodent and human beta-cells, as well as mouse islets. Insulinotropic actions of AVP were completely annulled by specific V1a or V1b receptor antagonists, and partially abolished by an oxytocin receptor antagonist. In addition, beta-cell insulin secretory actions of AVP were augmented by both IBMX (200 μM) and KCl (30 mM) and linked to significantly increased cAMP production and [Ca2+]i. AVP substantially increased proliferation of rodent and human beta-cells. Moreover, AVP fully protected against cytokine-induced beta-cell apoptosis. AVP had no effect on glucagon secretion. Immunohistochemical examination of beta- and alpha-cells revealed co-expression of AVP with glucagon, and particularly insulin. Finally, administration of AVP in combination with glucose to mice significantly reduced blood glucose, which was associated with increased plasma insulin. These data indicate that AVP possesses novel and potentially important effects on pancreatic endocrine function. Understanding disturbances in islet AVP receptor signalling could reveal insight into the beta-cell defects associated with diabetes.



中文翻译:

胰岛中的加压素受体增强葡萄糖耐量,胰岛β细胞分泌功能,增殖和存活

精氨酸加压素(AVP)是垂体后叶分泌的一种肽,主要被认为是一种参与调节体液平衡和渗透压的激素。然而,最近的证据表明,垂体后叶激素可对内分泌胰腺功能发挥重要作用。在本研究中,鼠胰岛以及啮齿动物BRIN BD11和人1.1B4β细胞中均证实了AVP受体的存在,即Avpr1a(V1a),Avpr1b(V1b)和Avpr2(V2)。除此之外,AVP还显示出明显的浓度依赖性(10 -12 – 10 -6 M)增加从啮齿动物和人β细胞以及小鼠胰岛释放的胰岛素。AVP的促胰岛素作用被特定的V1a或V1b受体拮抗剂完全废除了,而催产素受体拮抗剂则部分废除了。此外,IBMX(200μM)和KCl(30 mM)都增强了AVP的β细胞胰岛素分泌作用,并与cAMP产生和[Ca 2+ ] i的显着增加有关。。AVP大大增加了啮齿动物和人类β细胞的增殖。此外,AVP可以完全防止细胞因子诱导的β细胞凋亡。AVP对胰高血糖素的分泌没有影响。β和α细胞的免疫组织化学检查显示AVP与胰高血糖素,特别是胰岛素共表达。最后,与小鼠联合使用AVP和葡萄糖可显着降低血糖,这与血浆胰岛素增加有关。这些数据表明,AVP对胰腺内分泌功能具有新颖且潜在的重要作用。了解胰岛AVP受体信号传导的紊乱可以揭示对与糖尿病相关的β细胞缺陷的见解。

更新日期:2019-01-21
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