Proper release of insulin from pancreatic islets of Langerhans is essential for maintaining glucose homeostasis. For full efficacy, both the pattern and the amount of hormone release are critical. It is therefore important to understand how insulin levels are secreted from single islets in both a quantitative fashion and in a manner that resolves temporal dynamics. In this study, we describe a microfluidic analytical system that can both quantitatively monitor insulin secretion from single islets while simultaneously maintaining high temporal sampling to resolve dynamics of release. We have applied this system to determine the acute and chronic effects of a recently-identified lipid, 5-palmitic acid hydroxy stearic acid (5-PAHSA), which is a member of the fatty acid hydroxy fatty acid class of lipids that are upregulated in healthy individuals. Chronic incubation (48 h) with 5-PAHSA significantly increased glucose-stimulated insulin secretion (GSIS) in murine islets compared to chronic incubation without the lipid or in the presence of palmitic acid (PA). The studies were continued in human islets from both healthy donors and donors diagnosed with type 2 diabetes mellitus (T2DM). Total amounts of GSIS were not only augmented in islets that were chronically incubated with 5-PAHSA, but the dynamic insulin release profiles also improved as noted by more pronounced insulin oscillations. With this quantitative microfluidic system, we have corroborated the anti-diabetic effects of 5-PAHSA by demonstrating improved islet function after chronic incubation with this lipid via improved oscillatory dynamics along with higher basal and peak release rates.

中文翻译：

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微流控定量测量朗格汉斯岛单个胰岛对5-棕榈酸羟基硬脂酸的胰岛素释放动力学†

从郎格罕氏胰岛中正确释放胰岛素对于维持葡萄糖稳态是必不可少的。为了发挥全部功效，激素释放的方式和数量均至关重要。因此，重要的是要了解如何以定量方式和解决时间动态的方式从单个胰岛分泌胰岛素水平。在这项研究中，我们描述了一种微流体分析系统，该系统既可以定量监测单个胰岛的胰岛素分泌，又可以同时维持较高的时间采样以解决释放动力学问题。我们已应用该系统来确定最近确定的脂质5-棕榈酸羟基硬脂酸（5-PAHSA）的急性和慢性作用，该脂质是在脂肪中上调的脂肪酸羟基脂肪酸类别的成员健康的个体。与没有脂质或存在棕榈酸（PA）的长期孵育相比，与5-PAHSA的长期孵育（48 h）显着增加了小鼠胰岛中葡萄糖刺激的胰岛素分泌（GSIS）。这项研究在健康供体和被诊断患有2型糖尿病（T2DM）的供体的人类胰岛中继续进行。GSIS的总量不仅增加了与5-PAHSA长期孵育的胰岛的数量，而且动态胰岛素释放曲线也得到了改善，胰岛素振荡更为明显。通过这种定量的微流体系统，我们证明了与该脂质长期温育后胰岛功能的改善，从而证实了5-PAHSA的抗糖尿病作用通过改进的振荡动力学以及更高的基础和峰值释放速率。