In Silico Exploration Of Glyphosate's Binding Affinity And Inhibitory Effects On Key Metabolic Enzymes Implicated In Type 2 Diabetes Pathogenesis
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Abstract
The widespread use of glyphosate, a prominent herbicide, has raised concerns regarding its potential impact on human health, particularly in relation to metabolic disorders like Type 2 Diabetes (T2DM). This study presents an in-depth in silico exploration of glyphosate's interaction with key metabolic enzymes implicated in T2DM pathogenesis, providing insights into the molecular mechanisms that might underlie glyphosate-induced metabolic dysregulation.
Utilizing advanced computational modeling techniques, including molecular docking and dynamic simulations, we systematically investigated the binding affinity of glyphosate to a series of enzymes integral to glucose metabolism and insulin signaling pathways. These enzymes include glucokinase, insulin receptor, protein kinase B (Akt), and phosphoenolpyruvate carboxykinase (PEPCK), among others. The study aimed to elucidate the potential inhibitory effects of glyphosate on these enzymes, thereby implicating its role in disrupting normal metabolic processes.
Our results demonstrate a significant binding affinity of glyphosate to these enzymes, with binding patterns suggesting possible competitive or allosteric inhibition. The molecular docking scores indicated a strong interaction, especially with the insulin receptor and Akt, which are crucial for insulin signaling and glucose uptake. Furthermore, dynamic simulation analyses revealed conformational changes in the enzyme structures upon glyphosate binding, potentially affecting their functional activity.
These findings suggest a novel mechanism by which glyphosate exposure could contribute to the development of insulin resistance, a key feature of T2DM. The study highlights the importance of considering environmental factors like herbicide exposure in the etiology of metabolic diseases. It also underscores the potential of in silico methods as powerful tools in toxicological research, enabling the prediction and analysis of biochemical interactions at a molecular level.
While our study provides compelling theoretical evidence, it also emphasizes the need for experimental validation. Further research, both in vitro and in vivo, is essential to confirm the biological relevance of these findings and to understand the broader implications of glyphosate exposure on human health, particularly in the context of increasing global rates of T2DM
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