Analysis of Oxidative Stress Response with Anti-diabetic Treatment

Abstract

Among the three types of diabetes, type 2 diabetes originates from insulin resistance and is closely associated with physical inactivity, excess body weight, and hyperglycemia. Recent studies have shown that oxidative stress (OS), which is the imbalance between the production of reactive oxygen species and antioxidant defense mechanisms, can potentially affect the rate of restoration of glucose homeostasis, and hence type 2 diabetes. A cellular antioxidant, glutathione, which is a marker for oxidative stress in cells, has shown significant impact on the restoration rate of glucose during anti-diabetic treatment. The ratio of reduced to oxidised glutathione or the glutathione redox potential is believed to be a major driving factor of biological process, even though a theoretical explanation is absent for supporting this claim. This study focuses on the widely accepted fact that the ratio of reduced to oxidised glutathione concentrations is tightly maintained in cells, and very often the ratio is used as a marker for OS. A theoretical framework for the glutathione dynamics in RBCs, using simple mechanistic models of glutathione metabolism, is constructed based on the kinetics of the enzymes involved. The current work addresses the validity of using the ratio as a measure of OS and importance of the enzymes in glutathione redox system. Emerging from the hypothesis that the concentration of oxidised glutathione is constant at steady state, we propose a phenomenological model, along with the mechanistic models, for the relationship between blood glucose and glutathione concentrations at steady state. The model essentially captures the link between diabetes and OS, and can predict the recovery of individual glycemic status, during anti-diabetic treatment, to a great extent.