Oxidant Antioxidant Balance in β-Cells Predicting Insulin Secretion Impairment under POP Exposure

Abstract

Diabetes mellitus, a leading global health concern, is characterized by impaired insulin secretion and β-cell dysfunction. Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a significant role in this dysfunction. Persistent organic pollutants (POPs) such as PCB-153 and p,p'-DDE, which bioaccumulate in human tissues, have been identified as environmental agents that exacerbate oxidative stress, contributing to β-cell failure and the progression of diabetes. This study presents a mathematical model that simulates the interactions between ROS production, antioxidant depletion, and insulin secretion in pancreatic β-cells under varying levels of POP exposure. The model incorporates the dynamics of key antioxidants like glutathione (GSH) and catalase, and simulates the effects of antioxidant therapies such as N-acetyl-L-cysteine (NAC). Simulation results reveal that both low and high levels of POP exposure lead to significant ROS accumulation, GSH depletion, and reduced insulin secretion. Importantly, NAC treatment mitigates oxidative stress, restoring insulin secretion and delaying GSH depletion. The model highlights the critical role of antioxidants in protecting β-cells from oxidative damage and offers a predictive framework for assessing the long-term impacts of environmental pollutants on diabetes risk. These findings underscore the therapeutic potential of antioxidant treatments and the need for environmental pollutant regulation to reduce diabetes prevalence.