Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets
Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets
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DOI：
10.1016/s0303-7207(02)00051-5
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发表时间：
2002-06-14
影响因子：
4.1
通讯作者：
Jones, PM
中科院分区：
文献类型：
--
作者：
Hauge-Evans, AC;Squires, PE;Jones, PM
与在组织培养塑料上作为单层生长的MIN 6细胞相比，通过在明胶基质上培养而配置为细胞聚集体的MIN 6细胞（假胰岛）的胰岛素分泌增强，表明β细胞与β细胞接近对于胰岛素释放的重要性。在这项研究中，我们已经表明，葡萄糖诱导的胰岛素从假胰岛的双相释放，而相当于单层细胞的反应的幅度和持续时间大大减少。嘌呤能激动剂与β细胞间的细胞间通讯有关，因此我们研究了与胰岛素共同释放的腺嘌呤核苷酸是否负责增强假胰岛的分泌反应。我们已经证明，MIN 6细胞表达嘌呤能A（1）和P2 Y受体，腺嘌呤核苷酸增加[Ca（2+）]（i），激动剂的效力为ATP > ADP > AMP。然而，无论是苏拉明还是更具选择性的A1拮抗剂1，3-二丙基-8-环戊基黄嘌呤都不能减少葡萄糖诱导的假胰岛胰岛素分泌，并且用一系列腺嘌呤核苷酸刺激单层细胞不能增强葡萄糖诱导的分泌。这些结果表明，MIN 6假胰岛分泌增强不是由于腺嘌呤核苷酸的旁分泌/自分泌作用增加。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Insulin secretion from MIN6 cells configured as cell aggregates by culture on a gelatin substrate (pseudoislets) is enhanced compared to that of MIN6 cells grown as monolayers on tissue culture plastic, indicating the importance of beta-cell-to-beta-cell proximity for insulin release. In this study we have shown that glucose induced a biphasic release of insulin from pseudoislets, whereas the amplitude and duration of the responses of equivalent monolayer cells were much reduced. Purinergic agonists have been implicated in intercellular communication between beta-cells, so we investigated whether adenine nucleotides co-released with insulin are responsible for the enhanced secretory responses of pseudoislets. We have demonstrated that MIN6 cells express purinergic A(1) and P2Y receptors, and that adenine nucleotides increased [Ca(2+)](i) with an efficacy of agonists being ATP > ADP > AMP. However, neither suramin nor the more selective A, antagonist 1,3-dipropyl-8-cyclopentylxanthine reduced glucose-induced insulin secretion from pseudoislets, and stimulation of monolayer cells with a range of adenine nucleotides did not enhance glucose-induced secretion. These results suggest that enhanced secretion from MIN6 pseudoislets is not due to increased paracrine/autocrine action of adenine nucleotides. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.