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

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

  • Pestic Biochem Physiol. 2024 Sep:204:106098. doi: 10.1016/j.pestbp.2024.106098.
Yuchao Guo 1,  Dandan Gu 1,  Emmanuel Sunday Okeke 2,  Weiwei Feng 3,  Yao Chen 1,  Guanghua Mao 1,  Liuqing Yang 3,  Xiangyang Wu 4,  Ting Zhao 5
Affiliations

Affiliations

  • 1 School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
  • 2 School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China; Department of Biochemistry, Faculty of Biological Science & Natural Science Unit, School of General Studies, University of Nigeria, Nsukka, Enugu State 410001, Nigeria.
  • 3 School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
  • 4 School of the Environment, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China. Electronic address: wuxy@ujs.edu.cn.
  • 5 School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China. Electronic address: zhaoting@ujs.edu.cn.
PMID: 39277407 DOI: 10.1016/j.pestbp.2024.106098
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.

Keywords

AMPKα pathway: IRS1/PI3K/AKT pathway; Fenitrothion; Glucose metabolism; Toxicity.

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