Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell
Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell
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DOI：
10.1007/s00125-013-3019-5
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发表时间：
2013-12-01
期刊：
影响因子：
8.2
通讯作者：
Thorn, Peter
中科院分区：
文献类型：
--
作者：
Low, Jiun T.;Mitchell, Justin M.;Thorn, Peter
在分散的单个β细胞中，每个细胞对葡萄糖的反应是异质的。相比之下，在胰岛内，细胞与细胞的通讯导致葡萄糖诱导更均匀的反应。例如，NAD（P）H和钙的增加在胰岛细胞中相对均匀。这些数据表明，胰岛内单个β细胞的胰岛素分泌也应该是相对均匀的。本研究的目的是通过确定胰岛内单细胞胰岛素反应的葡萄糖依赖性来验证这一假设。双光子显微镜用于检测葡萄糖诱导的完整小鼠胰岛β细胞内单个胰岛素颗粒的融合。首先，我们验证了我们的分析，并表明整个胰岛分泌胰岛素的测量可以用颗粒融合事件的时间过程和数量来解释。观察随后的颗粒融合模式的分析表明，细胞募集是一个重要因素，占从3到20 mmol/l的葡萄糖增加了四倍。然而，主要因素是调节每个细胞内颗粒融合事件的数量，在3至20 mmol/l葡萄糖的范围内，颗粒融合事件的数量增加了9倍。进一步的分析表明，两种类型的颗粒融合事件发生：“完全融合”和“吻和运行”。我们发现，每种类型的融合的相对频率是独立的葡萄糖浓度，因此不是一个因素，在控制胰岛素分泌。在胰岛内，葡萄糖发挥其主要作用，通过增加细胞内的胰岛素颗粒融合事件的数量。
In dispersed single beta cells the response of each cell to glucose is heterogeneous. In contrast, within an islet, cell-to-cell communication leads to glucose inducing a more homogeneous response. For example, increases in NAD(P)H and calcium are relatively uniform across the cells of the islet. These data suggest that secretion of insulin from single beta cells within an islet should also be relatively homogeneous. The aim of this study was to test this hypothesis by determining the glucose dependence of single-cell insulin responses within an islet.Two-photon microscopy was used to detect the glucose-induced fusion of single insulin granules within beta cells in intact mouse islets.First, we validated our assay and showed that the measures of insulin secretion from whole islets could be explained by the time course and numbers of granule fusion events observed. Subsequent analysis of the patterns of granule fusion showed that cell recruitment is a significant factor, accounting for a fourfold increase from 3 to 20 mmol/l glucose. However, the major factor is the regulation of the numbers of granule fusion events within each cell, which increase ninefold over the range of 3 to 20 mmol/l glucose. Further analysis showed that two types of granule fusion event occur: 'full fusion' and 'kiss and run'. We show that the relative frequency of each type of fusion is independent of glucose concentration and is therefore not a factor in the control of insulin secretion.Within an islet, glucose exerts its main effect through increasing the numbers of insulin granule fusion events within a cell.