Importance of cell-matrix interactions in rat islet β-cell secretion in vitro -: Role of α6β1 integrin
Importance of cell-matrix interactions in rat islet β-cell secretion in vitro -: Role of α6β1 integrin
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DOI：
10.2337/diabetes.49.2.233
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发表时间：
2000-02-01
期刊：
影响因子：
7.7
通讯作者：
Rouiller, DG
中科院分区：
文献类型：
--
作者：
Bosco, D;Meda, P;Rouiller, DG
人们早就认识到，胰岛细胞的功能在体外会迅速改变，但当细胞分层在确定的细胞外基质上时，至少可以部分维持。目前的工作解决了短期细胞-基质相互作用对胰岛β细胞功能的影响，并首次深入了解了这些相互作用的分子基础。当原代大鼠β细胞附着在由大鼠癌细胞系（804G）产生的基质上时，对促分泌剂的胰岛素分泌反应增加。这种变化是活跃分泌β细胞比例增加和每个活跃细胞分泌胰岛素量增加的结果，如使用反向溶血斑块试验所示。反过来，分泌剂增强了β细胞在基质上的扩散或变平，变平的细胞比圆形细胞分泌更多的胰岛素。利用间接免疫荧光技术，发现1)α 6 β 1整合素原位存在于胰岛细胞表面；2)α 6 β 1在纯化的β细胞中表达是异质的，并被胰岛素分泌物上调；3)α 6 β 1在扩散细胞中表达较高；4)抗α 6 β 1特异性抗体减少扩散。这些观察结果表明，胰岛细胞-基质相互作用可以改善胰岛素细胞对葡萄糖的敏感性，并且至少部分是由α 6 β 1整合素介导的，这表明通过α 6 β 1整合素介导的外向内信号传导在调节β细胞功能中起着重要作用。
It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provides first insight into the molecular basis of these interactions. When primary rat beta-cells were allowed to attach to a matrix produced by a rat carcinoma cell line (804G), there was an increased insulin secretory response to secretagogues. This change was the result of an increase in the proportion of actively secreting beta-cells and in the amount of insulin secreted per active cell, as shown using the reverse hemolytic plaque assay. In turn, the spreading or flattening of beta-cells on this matrix was enhanced by secretagogues, and flattened cells secreted more insulin than rounded cells. Using indirect immunofluorescence, it was found that 1) alpha 6 beta 1 integrins are present at the surface of islet cells in situ, 2) alpha 6 beta 1 expression is heterogeneous among purified beta-cells and is upregulated by insulin secretagogues, 3) alpha 6 beta 1 expression is higher in spreading cells, and 4) anti-alpha 6 beta 1-specific antibodies decrease spreading. These observations demonstrate that islet cell-matrix interactions can improve the sensitivity of insulin cells to glucose and are mediated, at least in part, by alpha 6 beta 1 integrins, suggesting that outside-in signaling through alpha 6 beta 1 integrin plays a major role in the regulation of beta-cell function.