In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution.
In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution.
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DOI：
10.1002/adbi.201900291
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发表时间：
2020-03
影响因子：
4.1
通讯作者：
Frey O
中科院分区：
文献类型：
--
作者：
Misun PM;Yesildag B;Forschler F;Neelakandhan A;Rousset N;Biernath A;Hierlemann A;Frey O
胰岛素响应于升高的葡萄糖水平以双相和脉动方式从胰岛释放。这种高度动态的胰岛素释放可以用胰岛灌注测定法在体外研究。在此，提出了一种新的平台，以进行葡萄糖刺激的胰岛素分泌（GSIS）测定与单个胰岛研究在高时间分辨率的胰岛素释放的动力学。开发了标准化的人类胰岛模型，并设计了基于微流体悬滴的灌注系统，该系统有利于快速葡萄糖转换、最小样品稀释、低分析物分散和短采样间隔。人胰岛微组织具有稳健和长期的葡萄糖响应性，并表现出可再现的动态GSIS，具有突出的第一阶段和持续的脉动第二阶段。与合并胰岛的灌注相比，单个胰岛微组织的灌注产生更高的峰值分泌速率、在胰岛素释放的第一和第二阶段期间更高的分泌以及在第二阶段期间更明确的脉动。开发的平台能够研究化合物对胰岛素分泌两个阶段的影响，如两类胰岛素分泌物所示。它为研究生理相关的动态胰岛素分泌提供了一种新的工具，具有很低的样品间变化和高的时间分辨率。
Insulin is released from pancreatic islets in a biphasic and pulsatile manner in response to elevated glucose levels. This highly dynamic insulin release can be studied in vitro with islet perifusion assays. Herein, a novel platform to perform glucose-stimulated insulin secretion (GSIS) assays with single islets is presented for studying the dynamics of insulin release at high temporal resolution. A standardized human islet model is developed and a microfluidic hanging-drop-based perifusion system is engineered, which facilitates rapid glucose switching, minimal sample dilution, low analyte dispersion, and short sampling intervals. Human islet microtissues feature robust and long-term glucose responsiveness and demonstrate reproducible dynamic GSIS with a prominent first phase and a sustained, pulsatile second phase. Perifusion of single islet microtissues produces a higher peak secretion rate, higher secretion during the first and second phases of insulin release, as well as more defined pulsations during the second phase in comparison to perifusion of pooled islets. The developed platform enables to study compound effects on both phases of insulin secretion as shown with two classes of insulin secre-tagogs. It provides a new tool for studying physiologically relevant dynamic insulin secretion at comparably low sample-to-sample variation and high temporal resolution.
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影响因子：
6.1
作者：
de Groot TE;Veserat KS;Berthier E;Beebe DJ;Theberge AB
通讯作者：
Theberge AB
影响因子：
--
作者：
Buchwald P
通讯作者：
Buchwald P
影响因子：
7.4
作者：
Dishinger, John F.;Reid, Kendra R.;Kennedy, Robert T.
通讯作者：
Kennedy, Robert T.
DOI：
10.1039/c6an01055e
发表时间：
2016-10-21
期刊：
The Analyst
影响因子：
--
作者：
Brooks JC;Ford KI;Holder DH;Holtan MD;Easley CJ
通讯作者：
Easley CJ
影响因子：
3.3
作者：
Cabrera, Over;Jacques-Silva, M. Caroline;Caicedo, Alejandro
通讯作者：
Caicedo, Alejandro