Impact of Glyphosate on the Development of Insulin Resistance in Experimental Diabetic Rats: Role of NFκB Signalling Pathways
Monisha Prasad,
Mansour K. Gatasheh,
Mohammad A. Alshuniaber,
Rajapandiyan Krishnamoorthy,
Ponnulakhmi Rajagopal,
Kalaiselvi Krishnamoorthy,
Vijayalakshmi Periyasamy,
Vishnu Priya Veeraraghavan,
Selvaraj Jayaraman
Affiliations
Monisha Prasad
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospitals, Saveetha University, Chennai 600077, India
Mansour K. Gatasheh
Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Mohammad A. Alshuniaber
Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia
Rajapandiyan Krishnamoorthy
Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia
Ponnulakhmi Rajagopal
Department of Central Research Laboratory, Meenakshi Ammal Dental College and Hospitals, Chennai 600095, India
Kalaiselvi Krishnamoorthy
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospitals, Saveetha University, Chennai 600077, India
Vijayalakshmi Periyasamy
Department of Biotechnology and Bioinformatics, Holy Cross College, Trichy 620002, India
Vishnu Priya Veeraraghavan
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospitals, Saveetha University, Chennai 600077, India
Selvaraj Jayaraman
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospitals, Saveetha University, Chennai 600077, India
Glyphosate, an endocrine disruptor, has an adverse impact on human health through food and also has the potential to produce reactive oxygen species (ROS), which can lead to metabolic diseases. Glyphosate consumption from food has been shown to have a substantial part in insulin resistance, making it a severe concern to those with type 2 diabetes (T2DM). However, minimal evidence exists on how glyphosate impacts insulin-mediated glucose oxidation in the liver. Hence the current study was performed to explore the potential of glyphosate toxicity on insulin signaling in the liver of experimental animals. For 16 weeks, male albino Wistar rats were given 50 mg, 100 mg and 250 mg/kg b. wt. of glyphosate orally. In the current study, glyphosate exposure group was linked to a rise in fasting sugar and insulin as well as a drop in serum testosterone. At the same time, in a dose dependent fashion, glyphosate exposure showed alternations in glucose metabolic enzymes. Glyphosate exposure resulted in a raise in H2O2 formation, LPO and a reduction in antioxidant levels those results in impact on membrane integrity and insulin receptor efficacy in the liver. It also registered a reduced levels of mRNA and protein expression of insulin receptor (IR), glucose transporter-2 (GLUT2) with concomitant increase in the production of proinflammatory factors such as JNK, IKKβ, NFkB, IL-6, IL-1β, and TNF-α as well as transcriptional factors like SREBP1c and PPAR-γ leading to pro-inflammation and cirrhosis in the liver which results in the development of insulin resistance and type 2 diabetes. Our present findings for the first time providing an evidence that exposure of glyphosate develops insulin resistance and type 2 diabetes by aggravating NFkB signaling pathway in liver.
