Abstract：
Epidemiological studies have suggested a correlation between bisphenol A (BPA) and type 2 diabetes (T2DM). The effects of BPA on β-cell dysfunction may reveal the risks from an in vitro perspective. We used the rat insulinoma (INS-1) cell lines (a type of β-cells) to set up normal or damaged models (DM), which were exposed to various concentrations of BPA (0.001, 0.01, 0.1, 1, 10 and 100 μM). An increase in reactive oxygen species (ROS) and apoptosis, and a decrease in cell viability were observed in INS-1 cells exposed to high doses of BPA for 48 h. Interestingly, exposure to lower doses of BPA for 24 h resulted in increased ROS levels and apoptosis rates in INS-1 in the DM group, along with decreased cell viability, suggesting that BPA exerts toxicity to INS-1 cells, particularly to the DM group. Insulin levels and Glut2 expression, glucose consumption, intracellular Ca2+ and insulin secretion were increased in INS-1 cells after 48 h exposure to high dose of BPA. Stronger effects were observed in the DM group, even those exposed to low doses of BPA for 24 h. Moreover, BPA inhibited high glucose-stimulated insulin secretion in these cells. Our research suggests that low doses of BPA exacerbate the dysfunction caused by glucolipotoxicity, implying environmental BPA exposure poses a risk for individuals with prediabetes or T2DM.
摘要：
流行病学研究表明，双酚A（BPA）与2型糖尿病（T2DM）之间存在相关性。BPA对β细胞功能障碍的影响可能从体外角度揭示其风险。我们使用大鼠胰岛素瘤（INS-1）细胞系（一种β细胞）建立正常或受损的模型（DM），将其暴露于各种浓度的BPA(0.001、0.01、0.1、1、10和100μM)。活性氧（ROS）和细胞凋亡的增加，并且在暴露于高剂量BPA48小时的INS-1细胞中观察到细胞活力的降低。暴露于较低剂量的BPA24小时导致DM组INS-1中ROS水平和凋亡率增加，随着细胞活力的下降，表明BPA对INS-1细胞具有毒性，特别是DM组。胰岛素水平和Glut2表达，葡萄糖消耗，暴露于高剂量BPA48小时后，INS-1细胞的细胞内Ca2和胰岛素分泌增加。在DM组中观察到更强的效果,即使是那些暴露于低剂量双酚A24小时的人。此外，BPA抑制这些细胞中高葡萄糖刺激的胰岛素分泌。我们的研究表明，低剂量的BPA会加剧葡萄糖脂毒性引起的功能障碍，这意味着环境中的BPA暴露会给糖尿病前期或T2DM患者带来风险。
