Fenitrothion induces glucose metabolism disorders in rat liver BRL cells by inhibiting AMPKα and IRS1/PI3K/AKT signaling pathway

IF 4.2 1区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuchao Guo , Dandan Gu , Emmanuel Sunday Okeke , Weiwei Feng , Yao Chen , Guanghua Mao , Liuqing Yang , Xiangyang Wu , Ting Zhao
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Abstract

Fenitrothion (FNT) is a common organophosphorus pesticide that is widely used in both agricultural and domestic pest control. FNT has been frequently detected in various environmental media, including the human body, and is a notable contaminant. Epidemiological investigations have recently shown the implications of exposure to FNT in the incidence of various metabolic diseases, such as diabetes mellitus in humans, indicating that FNT may be a potential endocrine disruptor. However, the effects of FNT exposure on glucose homeostasis and their underlying mechanisms in model organisms remain largely unknown, which may limit our understanding of the health risks of FNT. In this study, FNT (4 5, 90, 180, and 4 50 μM) exposure model of rat hepatocytes (Buffalo Rat Liver, BRL cells) was established to investigate the effects and potential mechanisms of its toxicity on glucose metabolism. Several key processes of glucose metabolism were detected in this study. The results showed significantly increased glucose levels in the culture medium and decreased glycogen content in the FNT-exposed BRL cells. The results of quantitative real-time PCR and enzymology showed the abnormal expression of genes and activity/content of glucose metabolic enzymes involved in glucose metabolism, which might promote gluconeogenesis and inhibit glucose uptake, glycolysis, and glycogenesis. Furthermore, gluconeogenesis and glycolytic were carried out in the mitochondrial membrane. The abnormal of mitochondrial membrane potential may be a potential mechanism underlying FNT-induced glucose metabolism disorder. In addition, the mRNA and protein expression implicated that FNT may disrupt glucose metabolism by inhibiting the AMPKα and IRS1/PI3K/AKT signaling pathways. In conclusion, results provide in vitro evidence that FNT can cause glucose metabolism disorder, which emphasizes the potential health risks of exposure to FNT in inducing diabetes mellitus.

Abstract Image

杀螟松通过抑制 AMPKα 和 IRS1/PI3K/AKT 信号通路诱导大鼠肝脏 BRL 细胞葡萄糖代谢紊乱
杀螟松 (FNT) 是一种常见的有机磷杀虫剂,广泛用于农业和家庭害虫防治。FNT 经常在包括人体在内的各种环境介质中被检测到,是一种显著的污染物。最近的流行病学调查显示,接触 FNT 会影响人类糖尿病等各种代谢疾病的发病率,这表明 FNT 可能是一种潜在的内分泌干扰物。然而,暴露于 FNT 对模式生物体内葡萄糖稳态的影响及其内在机制在很大程度上仍然未知,这可能会限制我们对 FNT 健康风险的了解。本研究建立了大鼠肝细胞(水牛大鼠肝脏,BRL 细胞)的 FNT(4 5、90、180 和 4 50 μM)暴露模型,以研究其毒性对葡萄糖代谢的影响及其潜在机制。本研究检测了葡萄糖代谢的几个关键过程。结果表明,暴露于 FNT 的 BRL 细胞培养液中葡萄糖水平明显升高,糖原含量明显降低。实时定量 PCR 和酶学研究结果显示,参与葡萄糖代谢的基因表达和葡萄糖代谢酶的活性/含量异常,这可能会促进葡萄糖生成,抑制葡萄糖摄取、糖酵解和糖生成。此外,葡萄糖生成和糖酵解是在线粒体膜上进行的。线粒体膜电位异常可能是 FNT 诱导糖代谢紊乱的潜在机制。此外,mRNA 和蛋白质的表达表明,FNT 可能通过抑制 AMPKα 和 IRS1/PI3K/AKT 信号通路来破坏糖代谢。总之,研究结果提供了 FNT 可导致糖代谢紊乱的体外证据,强调了暴露于 FNT 在诱发糖尿病方面的潜在健康风险。
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来源期刊
CiteScore
7.00
自引率
8.50%
发文量
238
审稿时长
4.2 months
期刊介绍: Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance. Research Areas Emphasized Include the Biochemistry and Physiology of: • Comparative toxicity • Mode of action • Pathophysiology • Plant growth regulators • Resistance • Other effects of pesticides on both parasites and hosts.
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