Pituitary adenylate cyclase‐activating polypeptide (PACAP) is an islet substance serving as an intra‐islet amplifier Of glucose‐induced insulin secretion in rats

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is an islet substance serving as an intra‐islet amplifier Of glucose‐induced insulin secretion in rats
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垂体腺苷酸环化酶激活多肽(PACAP)是一种胰岛物质,作为葡萄糖诱导的大鼠胰岛素分泌的胰岛内放大器

DOI:
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发表时间:
1997
期刊:
Journal of Physiology
影响因子:
--
通讯作者:
Yoshitomo Oka
Yoshitomo Oka
中科院分区:
--
文献类型:
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作者:
T. Yada;Masaya Sakurada;H. Ishihara;M. Nakata;S. Shioda;K. Yaekura;Noriaki Hamakawa;K. Yanagida;M. Kikuchi;Yoshitomo Oka

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1我们研究了具有38或27个残基的垂体腺苷酸环化酶激活多肽(PACAP-38或PACAP-27)是否作为大鼠葡萄糖诱导的胰岛素分泌的胰岛内调节剂。使用对PACAP-38和PACAP-27具有特异性的PACAP抗血清来中和胰岛中内源性PACAP的作用。使用单β细胞中胞质Ca 2+浓度([Ca 2 +]i)的响应,通过双波长Fura-2显微荧光测定法监测胰岛中的PACAP释放。通过逆转录-聚合酶链反应(RT-PCR)研究PACAP mRNA的表达,同时通过代谢标记和免疫印迹研究PACAP的表达。PACAP受体的定位进行了电化学研究。2分离胰岛的高糖刺激胰岛素释放被PACAP抗血清减弱,但未被非免疫血清减弱。3高糖胰岛培养液(Med)具有增加β细胞[Ca 2 +]i的能力,可被PACAP抗血清中和。PACAP抗血清也中和了合成的PACAP-38和PACAP-27的[Ca 2 +] i增加作用,但不能中和血管活性肠多肽(VIP)和胰高血糖素的[Ca 2 +] i增加作用。[4] Med和合成PACAP仅在刺激性葡萄糖浓度(而非基础葡萄糖浓度)存在下增加β细胞中的[Ca 2 +]i。相比之下,ATP,一种已知从β细胞释放的物质,在基础和刺激葡萄糖浓度下增加β细胞中的[Ca 2 +]i。5在胰岛和β细胞系MIN 6中检测到PACAP mRNA的表达和PACAP-38的生物合成。6在胰岛中观察到PACAP选择性I型受体的免疫反应性。7 [Ca 2 +]i测量结合使用胰岛素抗血清的免疫细胞化学显示大量葡萄糖无反应β细胞群,其中许多被PACAP-38募集到[Ca 2 +]i反应中。8这些结果表明,PACAP-38是一种新型胰岛物质,由胰岛细胞合成和释放,然后以自分泌和/或旁分泌方式增强和激发β细胞对葡萄糖的反应,从而放大葡萄糖诱导的胰岛胰岛素分泌。
1 We examined whether pituitary adenylate cyclase‐activating polypeptide with 38 or 27 residues (PACAP‐38 or PACAP‐27) serves as an intra‐islet regulator of glucose‐induced insulin secretion in rats. PACAP antiserum specific for PACAP‐38 and PACAP‐27 was used to neutralize the effect of endogenous PACAP in islets. PACAP release from islets was bioassayed using the response of cytosolic Ca2+ concentration ([Ca2+]i) in single β‐cells, monitored by dual‐wavelength fura‐2 microfluorometry. Expression of PACAP mRNA was studied by reverse transcription‐polymerase chain reaction (RT‐PCR), while expression of PACAP was studied by metabolic labelling and immunoblotting. Localization of PACAP receptors was studied immunohistochemically. 2 High glucose‐stimulated insulin release from isolated islets was attenuated by PACAP anti‐serum but not by non‐immune sera. 3 The islet incubation medium with high glucose (Med) possessed a capacity, which was neutralized by PACAP antiserum, to increase [Ca2+]i in β‐cells. PACAP antiserum also neutralized the [Ca2+]iincreasing action of synthetic PACAP‐38 and PACAP‐27, but not that of vasoactive intestinal polypeptide (VIP) and glucagon. 4 Both Med and synthetic PACAP increased [Ca2+]i in β‐cells only in the presence of stimulatory, but not basal, glucose concentrations. In contrast, ATP, a substance that is known to be released from β‐cells, increased [Ca2+]i in β‐cells at both basal and stimulatory glucose concentrations. 5 Expression of PACAP mRNA and biosynthesis of PACAP‐38 were detected in islets and a β‐cell line, MIN6. 6 Immunoreactivity for PACAP‐selective type‐I receptor was observed in islets. 7 [Ca2+]i measurements combined with immunocytochemistry with insulin antiserum revealed a substantial population of glucose‐unresponsive β‐cells, many of which were recruited by PACAP‐38 into [Ca2+]i responses. 8 These results indicate that PACAP‐38 is a novel islet substance that is synthesized and released by islet cells and then, in an autocrine and/or paracrine manner, potentiates and arouses β‐cells responses to glucose, thereby amplifying glucose‐induced insulin secretion in islets.
38 个氨基酸形式的垂体腺苷酸环化酶激活多肽可刺激 PC12 细胞中的双重信号级联反应并促进神经突生长。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
Deutsch,PJ;Sun,Y
通讯作者: Sun,Y
绵羊下丘脑中一种新型下丘脑肽——垂体腺苷酸环化酶激活多肽的免疫组织化学演示。
DOI: 10.1210/endo-127-1-264
发表时间: 1990
期刊: Endocrinology
影响因子: 4.8
作者:
Köves,K;Arimura,A;Somogyvári-Vigh,A;Vigh,S;Miller,J
通讯作者: Miller,J
DOI: 10.1016/0006-291x(89)91757-9
发表时间: 1989-10-16
影响因子: 3.1
作者:
MIYATA, A;ARIMURA, A;COY, DH
通讯作者: COY, DH