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地塞米松处理后分离的大鼠胰岛中神经肽Y、血管活性肠多肽和β-降钙素基因相关肽的肽含量及其信使核糖核酸

Peptide contents of neuropeptide Y, vasoactive intestinal polypeptide, and beta-calcitonin gene-related peptide and their messenger ribonucleic acids after dexamethasone treatment in the isolated rat islets of Langerhans.

作者信息

Jamal H, Jones P M, Byrne J, Suda K, Ghatei M A, Kanse S M, Bloom S R

机构信息

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

出版信息

Endocrinology. 1991 Dec;129(6):3372-80. doi: 10.1210/endo-129-6-3372.

Abstract

A number of neuropeptides including neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and beta-calcitonin gene related peptide (beta-CGRP) are known to influence insulin secretion. In order to investigate whether they might have a local autocrine/paracrine effect within the islets of Langerhans we screened isolated islets by Northern blot analysis and RIA for a number of peptides and found evidence for the presence of messenger RNA (mRNA) encoding NPY, VIP, and beta-CGRP. Dexamethasone treatment for 12 days increased the content of NPY, VIP, and beta-CGRP significantly from 1.3 +/- 0.3 to 19.8 +/- 1.6; 0.25 +/- 0.03 to 0.91 +/- 0.1; 2.2 +/- 0.2 to 4.8 +/- 0.1 fmol/islet respectively, mean +/- SEM (n = 4, P less than 0.05) and remained elevated 24 h after recovery. However when the results were normalized and expressed as a ratio of insulin content only NPY and VIP were significantly raised. Five days post treatment VIP was still significantly elevated compared to controls. mRNA for NPY increased 10-fold and for VIP increased 2 1/2 times after dexamethasone whereas mRNA for beta-CGRP was not significantly different from controls. Neither capsaicin nor 6-hydroxydopamine affected islet content or message of NPY, VIP, and beta-CGRP. Immunoreactive NPY and its mRNA were detected in two cultured beta-cell lines, HIT T-15 and RIN m5F cells whereas VIP and beta-CGRP were undetectable. The local islet synthesis of neuropeptides, which are known to influence islet hormone release pharmacologically, suggests the possibility that they may play a role in intraislet paracrine regulation.

摘要

已知包括神经肽Y(NPY)、血管活性肠肽(VIP)和β-降钙素基因相关肽(β-CGRP)在内的多种神经肽会影响胰岛素分泌。为了研究它们是否可能在胰岛内具有局部自分泌/旁分泌作用,我们通过Northern印迹分析和放射免疫分析(RIA)对分离的胰岛进行了多种肽的筛选,发现了编码NPY、VIP和β-CGRP的信使核糖核酸(mRNA)存在的证据。地塞米松处理12天使NPY、VIP和β-CGRP的含量分别从1.3±0.3显著增加至19.8±1.6;0.25±0.03增加至0.91±0.1;2.2±0.2增加至4.8±0.1 fmol/胰岛,均值±标准误(n = 4,P<0.05),并且在恢复后24小时仍保持升高。然而,当结果进行归一化并表示为胰岛素含量的比值时,只有NPY和VIP显著升高。处理后5天,VIP与对照组相比仍显著升高。地塞米松处理后,NPY的mRNA增加了10倍,VIP的mRNA增加了2.5倍,而β-CGRP的mRNA与对照组无显著差异。辣椒素和6-羟基多巴胺均未影响胰岛中NPY、VIP和β-CGRP的含量或信息。在两种培养的β细胞系HIT T-15和RIN m5F细胞中检测到免疫反应性NPY及其mRNA,而未检测到VIP和β-CGRP。已知在药理上会影响胰岛激素释放的神经肽在胰岛内的局部合成表明它们可能在胰岛内旁分泌调节中发挥作用。

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