Dynamic In Silico Model of Type ۲ Diabetes Treated With Metformin Combined With Exercise: A Sobol Sensitivity Analysis

Background: The widespread adoption of a sedentary lifestyle characterized by the consumption of a high-energy diet combined with a lack of physical activity has resulted in a rise in the prevalence of metabolic disorders like type ۲ diabetes (T۲D) globally. The data published by the International Diabetes Federation (IDF) every year catches the attention of the world. Insulin resistance results in the dysregulation of the control mechanism that leads to T۲D. In addition to metformin as a globally prescribed drug, physical exercise is recommended for the treatment of T۲D as an alternative therapy. In today’s systems biology era, sensitivity analysis plays a major role in providing deeper insights into the metabolic insulin signalling pathways (ISPs). Methods: Here, the complex in silico dynamic model of the effect of alternative therapies on T۲D was examined. In order to obtain more quantitative information about the signal transduction network of the ISPs and their interaction, a global sensitivity analysis of the in silico model was carried out using the MATLAB tool. Results: This study sheds light on the effect of parameter perturbation on the ISP via GLUT۴ translocation in T۲D patients performing physical exercise and using metformin. It also allows for the selection of a variety of parameters for in vivo or in vitro studies in the future on the basis of the impact of parameter variations on each component of the pathway. Conclusion: The Sobol index for each condition was noted after introducing perturbations in the most sensitive parameters. These results can provide experimental guidance on how the variations in model inputs have affected the model outputs.