The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β‐cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β‐cell islets, large‐scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold‐free formation of densely packed β‐cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the β‐cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the β‐cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species‐induced caspase‐mediated pathway. The β‐cells' MAP might provide a potential new map in the pathophysiological mechanisms of β cells.

中文翻译：

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胰岛β细胞球体的微生理分析平台

糖尿病患者的标志是胰岛素分泌不足和胰高血糖素功能失调。了解朗格汉斯胰岛中胰岛素，胰高血糖素和其他激素的释放机制至关重要。尽管在糖尿病研究和实践中取得了显着进展，但仍缺乏可测量胰腺β细胞功能的健壮且可复制的模型。在这里，报道了一种微生理分析平台（MAP），该平台可实现胰腺β细胞胰岛的均匀3D球体形成，大规模形态学表型分析以及慢性血糖和血脂异常发展的基因表达图谱。MAP使无支架的密集堆积的β细胞球体（即110个生物反应器的多个阵列）形成，并在生理相关微环境的启发下被灌注流动网络包围。MAP允许对β细胞球体进行动态扰动，并精确控制血糖和血脂血症，这使我们能够确认高血糖和高血脂症下β细胞球体的细胞凋亡主要取决于活性氧诱导的胱天蛋白酶-介导的途径。β细胞的MAP可能为β细胞的病理生理机制提供潜在的新图谱。