Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose.
Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose.
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DOI：
10.1016/j.cmet.2016.06.020
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发表时间：
2016-09-13
期刊：
影响因子：
29
通讯作者：
Hodson DJ
中科院分区：
文献类型：
--
作者：
Johnston NR;Mitchell RK;Haythorne E;Pessoa MP;Semplici F;Ferrer J;Piemonti L;Marchetti P;Bugliani M;Bosco D;Berishvili E;Duncanson P;Watkinson M;Broichhagen J;Trauner D;Rutter GA;Hodson DJ
β细胞在朗格汉斯胰岛内的排列是通过产生节律性活动来释放胰岛素的关键。长期以来，人们一直怀疑单个β细胞在协调这些反应中的特殊作用，但没有直接证明。我们在这里表明β细胞群在原位操作上是异质的。胰岛功能结构的绘制揭示了具有起搏器特性的中枢细胞的存在，这些细胞在记录2至3小时的时间内保持稳定。通过双光遗传学/光药理学策略，中枢的沉默消除了胰岛对葡萄糖的协调反应，而特定刺激恢复了通讯模式。中枢代谢适应并被促炎和糖脂毒性损伤靶向，以诱导广泛的β细胞功能障碍。因此，胰岛由枢纽连接，其失败可能导致2型糖尿病。这些细胞被称为枢纽细胞，是正常胰岛素释放所必需的。枢纽细胞是高代谢和转录不成熟的枢纽细胞，被糖尿病环境靶向诱导胰岛衰竭。结合光遗传学和光药理学，Johnston等人表明，少数(1%-10%)β细胞对胰岛对葡萄糖的反应施加不成比例的控制。这些特化的细胞，被称为枢纽，是转录不成熟的和高度代谢的。它们在2型糖尿病期间的衰竭可能导致胰岛素分泌减少和葡萄糖稳态受损。
The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus. Optogenetic targeting reveals a pacemaker-like β cell subpopulation These cells, termed hubs, are required for normal insulin release Hubs are highly metabolic and transcriptionally immature Hubs are targeted by a diabetic milieu to induce islet failure Combining optogenetics and photopharmacology, Johnston et al. show that a few (1%–10%) β cells exert disproportionate control over islet responses to glucose. These specialized cells, called hubs, are transcriptionally immature and highly metabolic. Their failure during type 2 diabetes mellitus may lead to reduced insulin secretion and impaired glucose homeostasis.
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