Local Integrin Activation in Pancreatic β Cells Targets Insulin Secretion to the Vasculature
Local Integrin Activation in Pancreatic β Cells Targets Insulin Secretion to the Vasculature
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DOI：
10.1016/j.celrep.2018.08.035
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发表时间：
2018-09-11
期刊：
影响因子：
8.8
通讯作者：
Thorn, Peter
中科院分区：
文献类型：
--
作者：
Gan, Wan Jun;Oanh Hoang Do;Thorn, Peter
细胞外基质（ECM）通过整合素激活严重影响β细胞功能。但这些ECM作用是否像在上皮细胞中一样驱动b细胞的空间组织尚不清楚。本研究表明，在朗格汉斯胰岛内，b细胞的局灶性粘附激活只发生在它们接触毛细血管表面的地方。在培养的b细胞中，3D绘图显示，在细胞接触ecm包被的盖片处，胰岛素颗粒融合富集，这取决于β 1整合素受体的激活。在E-cadherin和纤连蛋白的微接触印刷条纹上培养表明，b细胞在纤连蛋白条纹处的接触选择性地激活了局灶性粘附，并丰富了胞外机制和胰岛素颗粒融合。在高糖环境中培养细胞，作为糖毒性模型，可以消除颗粒靶向性。我们得出结论，局部整合素激活的目标是胰岛素分泌到胰岛毛细血管。这种机制可能对胰岛功能很重要，并可能在疾病中发生改变。
The extracellular matrix (ECM) critically affects beta cell functions via integrin activation. But whether these ECM actions drive the spatial organization of b cells, as they do in epithelial cells, is unknown. Here, we show that within islets of Langerhans, focal adhesion activation in b cells occurs exclusively where they contact the capillary ECM (vascular face). In cultured b cells, 3D mapping shows enriched insulin granule fusion where the cells contact ECM-coated cover-slips, which depends on beta 1 integrin receptor activation. Culture on micro-contact printed stripes of E-cadherin and fibronectin shows that b cell contact at the fibronectin stripe selectively activates focal adhesions and enriches exocytic machinery and insulin granule fusion. Culture of cells in high glucose, as a model of glucotoxicity, abolishes granule targeting. We conclude that local integrin activation targets insulin secretion to the islet capillaries. This mechanism might be important for islet function and may change in disease.