Bisphenol F (BPF) is a substitute of bisphenol A in the production of epoxy resin and polycarbonate. Its extensive use in consumer products leads to a wide human exposure at high levels. Although the adverse effects of BPF on animal health are of increasing public concern, its risks on systematic glucose metabolism and blood glucose concentrations still remain largely unknown. Using zebrafish larvae as the model animal, we investigated the disturbance of BPF exposure on glucose metabolism and the underlying mechanisms. Zebrafish larvae at 96 h post fertilization were exposed to 0.1, 1, 10, and 100 μg/L of BPF for 48 h. Compared with the control group, glucose levels of larvae increased significantly in the 10 and 100 μg/L exposure groups, which are associated with enhancement of gluconeogenesis and suppression of glycolysis induced by high doses of BPF. Additionally, both mRNA expressions and protein levels of insulin increased significantly in the 10 and 100 μg/L exposure groups, while transcription levels of genes encoding insulin receptor substrates decreased significantly in these groups, indicating a possibly decreased insulin sensitivity due to impairment of insulin signaling transduction downstream of insulin receptor. Further, compared with BPF alone, co-exposure of larvae to BPF and rosiglitazone, an insulin sensitizer, significantly attenuates increases in both glucose levels and mRNA expressions of a key gluconeogenesis enzyme. Our data therefore indicate impairing insulin signaling transduction may be the main mechanism through which BPF disrupts glucose metabolism and induces hyperglycemia. Results of the present study inform the health risk assessment of BPF and also suggest the use of zebrafish larvae in large-scale screening of chemicals with possible glucose metabolism disturbing effect.

双酚F（BPF）在环氧树脂和聚碳酸酯的生产中是双酚A的替代品。它在消费产品中的广泛使用导致高水平的人为暴露。尽管BPF对动物健康的不利影响越来越引起公众关注，但其对系统性葡萄糖代谢和血糖浓度的风险仍然未知。以斑马鱼幼虫为模型动物，我们研究了BPF暴露对葡萄糖代谢的干扰及其潜在机制。受精后96小时的斑马鱼幼虫暴露于0.1、1、10和100μg/ L的BPF中48小时。与对照组相比，在10和100μg/ L的暴露组中，幼虫的葡萄糖水平显着增加，它们与高剂量BPF诱导的糖原异生的增强和糖酵解的抑制有关。此外，在10和100μg/ L暴露组中，胰岛素的mRNA表达和蛋白质水平均显着增加，而在这些组中，编码胰岛素受体底物的基因的转录水平显着降低，表明由于胰岛素信号传导受损，胰岛素敏感性可能降低胰岛素受体下游的转导。此外，与单独使用BPF相比，将幼虫与BPF和罗格列酮（一种胰岛素增敏剂）共同暴露会显着减弱关键糖异生酶的葡萄糖水平和mRNA表达的增加。因此，我们的数据表明，胰岛素信号转导受损可能是BPF破坏葡萄糖代谢并引起高血糖症的主要机制。本研究的结果为BPF的健康风险评估提供了依据，并且还建议使用斑马鱼幼虫大规模筛查可能干扰葡萄糖代谢的化学药品。