Impact of Glyphosate on the Development of Insulin Resistance in Experimental Diabetic Rats: Role of NFκB Signalling Pathways

Abstract

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.

Association of Lifetime Exposure to Glyphosate and Aminomethylphosphonic Acid (AMPA) with Liver Inflammation and Metabolic Syndrome at Young Adulthood: Findings from the CHAMACOS Study

“…In a study of male rats, Prasad et al. 33 found a dose-related increase in fasting blood glucose and serum insulin in glyphosate-exposed groups in comparison with controls. To our knowledge, the association of glyphosate with insulin resistance and other metabolic disorders has not been previously explored in human populations, although researchers have hypothesized that glyphosate has the potential to induce metabolic disease because of its ability to induce oxidative stress in preadipocytes and in other tissues.…”

“…20 Animal 24 – 28 and human 29 – 31 studies have suggested that exposure to glyphosate may be related to liver disease, and some researchers have hypothesized a potential relationship with metabolic disorders. 32 , 33 In the current study, we investigated the association of prenatal and childhood exposure to glyphosate and AMPA—as indicated by urinary concentrations and registry data of nearby agricultural use of glyphosate—with markers of liver inflammation and metabolic syndrome in young adults.…”

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

“…Multiple researchers have shown that oxidative stress, inflammatory response, and lipid metabolism disorder were the most common pathogenic features of GLY-induced liver injury. The overproduction of ROS could alter the levels and activities of antioxidants including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [75][76][77]. Oxidative stress can activate inflammatory reaction pathways leading to the production of proinflammatory factors (IL-1β, IL-6, IL-10, IFN-γ, TNF-α) [47,76,78,79].…”

“…The overproduction of ROS could alter the levels and activities of antioxidants including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [75][76][77]. Oxidative stress can activate inflammatory reaction pathways leading to the production of proinflammatory factors (IL-1β, IL-6, IL-10, IFN-γ, TNF-α) [47,76,78,79]. In addition, ROS and oxidative stress may result in lipid peroxidation or even oxidative damage of lipids [44,45].…”

Role of ceramides in diabetic foot ulcers (Review)

“…NFKBIB and NFKB are connected in the cytoplasm. Increased NFKBIB/NFKB signaling activity may be a significant factor in T2DM inflammation and insulin resistance ( 170 ). Fatty acyl-CoAs are an example of an inflammatory factor that activates NFKBIB kinase, phosphorylates NFKBIB and then translocates to the nucleus to bind to target genes, thus increasing the production of inflammatory cytokines that are involved in atherosclerosis (TNF, IL1B, IL6 and PKC) ( 171 , 172 ).…”