Measurement of the entrainment window of islets of Langerhans by microfluidic delivery of a chirped glucose waveform.
Measurement of the entrainment window of islets of Langerhans by microfluidic delivery of a chirped glucose waveform.
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DOI：
10.1039/c5ib00156k
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Roper MG
中科院分区：
文献类型：
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作者：
Dhumpa R;Truong TM;Wang X;Roper MG
在朗格汉斯的单个胰岛内，胰腺的内分泌部分、细胞内代谢物以及胰岛素分泌以约 5 分钟的周期振荡。在体内，还观察到周期为 5 – 15 分钟的脉动胰岛素振荡。为了在体内观察胰岛素的振荡，胰腺中的大多数胰岛必须同步其输出。众所周知，胰岛群可以通过单个胰岛夹带至低振幅葡萄糖振荡来同步，该振荡的周期接近胰岛的自然周期。然而，可以夹带胰岛的葡萄糖周期和幅度的范围尚未经过严格检查。为了找到可以夹带胰岛的葡萄糖周期范围，利用微流体系统产生并向胰岛群传递啁啾的葡萄糖波形，同时对它们各自的细胞内 [Ca2+] ([Ca2+]i) 振荡进行成像。应用幅度为 0.5、1 和 1.5 mM（高于中值 11 mM）的波形，同时扫描周期为 20 - 2 分钟。当葡萄糖波的周期在胰岛自然周期的 2 分钟内（通常接近 5 分钟）时，[Ca2+]i 的振荡最强。在长期和短期葡萄糖暴露期间分别观察到了 1:2 和 2:1 夹带的一些例子。这些结果揭示了胰岛行为的动态性质，并可能有助于理解体内观察到的动态。
Within single islets of Langerhans, the endocrine portion of the pancreas, intracellular metabolites, as well as insulin secretion, oscillates with a period of ~5 min. In vivo, pulsatile insulin oscillations are also observed with periods ranging from 5 – 15 minutes. In order for oscillations of insulin to be observed in vivo, the majority of islets in the pancreas must synchronize their output. It is known that populations of islets can be synchronized via entrainment of the individual islets to low amplitude glucose oscillations that have periods close to islets’ natural period. However, the range of glucose periods and amplitudes that can entrain islets has not been rigorously examined. To find the range of glucose periods that can entrain islets, a microfluidic system was utilized to produce and deliver a chirped glucose waveform to populations of islets while their individual intracellular [Ca2+] ([Ca2+]i) oscillations were imaged. Waveforms with amplitudes of 0.5, 1, and 1.5 mM above a median value of 11 mM were applied while the period was swept from 20 - 2 min. Oscillations of [Ca2+]i resonated the strongest when the period of the glucose wave was within 2 min of the natural period of the islets, typically close to 5 min. Some examples of 1:2 and 2:1 entrainment were observed during exposure to long and short glucose periods, respectively. These results shed light on the dynamic nature of islet behavior and may help to understand dynamics observed in vivo.