Abstract：
Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with the normal function of the endocrine system. EDCs are ubiquitous and can be found in a variety of consumer products such as food packaging materials, personal care and household products, plastic additives, and flame retardants. Over the last decade, the impact of EDCs on human health has been widely acknowledged as they have been associated with different endocrine diseases. Among them, a subset called metabolism-disrupting chemicals (MDCs) is able to promote metabolic changes that can lead to the development of metabolic disorders such as diabetes, obesity, hepatic steatosis, and metabolic syndrome, among others. Despite this, today, there are still no definitive and standardized in vitro tools to support the metabolic risk assessment of existing and emerging MDCs for regulatory purposes. Here, we evaluated the following two different pancreatic cell-based in vitro systems: the murine pancreatic β-cell line MIN6 as well as the human pancreatic β-cell line EndoC-βH1. Both were challenged with the following range of relevant concentrations of seven well-known EDCs: (bisphenol-A (BPA), bisphenol-S (BPS), bisphenol-F (BPF), perfluorooctanesulfonic acid (PFOS), di(2-ethylhexyl) phthalate (DEHP), cadmium chloride (CdCl2), and dichlorodiphenyldichloroethylene (DDE)). The screening revealed that most of the tested chemicals have detectable, deleterious effects on glucose-stimulated insulin release, insulin content, electrical activity, gene expression, and/or viability. Our data provide new molecular information on the direct effects of the selected chemicals on key aspects of pancreatic β-cell function, such as the stimulus-secretion coupling and ion channel activity. In addition, we found that, in general, the sensitivity and responses were comparable to those from other in vivo studies reported in the literature. Overall, our results suggest that both systems can serve as effective tools for the rapid screening of potential MDC effects on pancreatic β-cell physiology as well as for deciphering and better understanding the molecular mechanisms that underlie their action.
摘要：
内分泌干扰化学物质（EDC）是可以干扰内分泌系统正常功能的化学物质。EDC无处不在，可以在各种消费品中找到，例如食品包装材料，个人护理和家用产品，塑料添加剂,和阻燃剂。在过去的十年里，EDC对人类健康的影响已被广泛认可，因为它们与不同的内分泌疾病有关。其中,一个称为代谢破坏化学物质（MDC）的子集能够促进代谢变化，从而导致糖尿病等代谢紊乱的发展，肥胖，肝脂肪变性,代谢综合征,在其他人中。尽管如此,今天,目前还没有明确的标准化体外工具来支持现有和新出现的MDCs的代谢风险评估,以达到监管目的.这里,我们评估了以下两种不同的基于胰腺细胞的体外系统：鼠胰腺β细胞系MIN6以及人胰腺β细胞系EndoC-βH1。两者都受到以下7种众所周知的EDC相关浓度范围的挑战：（双酚A（BPA），双酚-S(BPS),双酚F(BPF),全氟辛烷磺酸(PFOS)，邻苯二甲酸二(2-乙基己基)酯(DEHP),氯化镉(CdCl2),和二氯二苯基二氯乙烯(DDE))。筛查显示，大多数测试的化学物质都可以检测到，对葡萄糖刺激的胰岛素释放的有害影响，胰岛素含量，电活动,基因表达，和/或生存能力。我们的数据为所选化学物质对胰腺β细胞功能关键方面的直接影响提供了新的分子信息。如刺激-分泌耦合和离子通道活性。此外,我们发现,总的来说,灵敏度和反应与文献报道的其他体内研究相当.总的来说,我们的结果表明,这两个系统都可以作为快速筛查MDC对胰腺β细胞生理学的潜在影响以及破译和更好地理解其作用背后的分子机制的有效工具.
