The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Anal Biochem. 2012 Apr 1;423(1):61-9. doi: 10.1016/j.ab.2012.01.014. Epub 2012 Jan 24.
β-Cell injury plays an important role in the development of type 1 and type 2 diabetes. Most of the β-cell bioassays depend on labeling or endpoint assessments that might not capture the true physiology or pathology of the injury process. In the current study, we dynamically detected a broad range of pathological and pharmacological responses to four toxicants (cytokine mixture, free fatty acid mixture, streptozotocin, and hydrogen peroxide) in living β-cells (INS-1E and MIN6) by a label-free, cell-based assay system named xCELLigence, codeveloped by ACEA Biosciences and Roche Diagnostics. Our results suggest that the impedance readout is highly sensitive and provides more information than some of the conventional endpoint cytotoxicity assays for β-cell injury such as the Cell Counting Kit-8 (CCK-8) and morphology measurements. Furthermore, this system was used to evaluate the anti-injury effects of glucagon-like peptide-1 (GLP-1) and its nonpeptidic mimetic Boc5 by monitoring responses to four toxicants in two β-cell lines. This study confirms that the protective property of Boc5 on β-cells is similar to that of GLP-1.
β 细胞损伤在 1 型和 2 型糖尿病的发生发展中起着重要作用。大多数β细胞生物测定依赖于标记或终点评估，而这些方法可能无法捕捉到损伤过程的真实生理学或病理学。在本研究中，我们通过 ACEA Biosciences 和 Roche Diagnostics 共同开发的一种无标记、基于细胞的测定系统 xCELLigence，动态检测了四种毒物（细胞因子混合物、游离脂肪酸混合物、链脲佐菌素和过氧化氢）对活β细胞（INS-1E 和 MIN6）的广泛病理和药理反应。我们的结果表明，阻抗读数非常敏感，比某些传统的β细胞损伤终点细胞毒性测定（如 Cell Counting Kit-8（CCK-8）和形态学测量）提供了更多信息。此外，该系统还用于通过监测两种β细胞系对四种毒物的反应来评估胰高血糖素样肽-1（GLP-1）及其非肽模拟物 Boc5 的抗损伤作用。本研究证实 Boc5 对β细胞的保护作用与 GLP-1 相似。
