Insulin Signaling Pathway Model in Adipocyte Cells.

backgroundWorldwide, type 2 diabetes mellitus (T2DM) is one of the most pervasive and fastgrowing disorders, bringing long-term adverse effects. T2DM arises from pancreatic β-cells deficiency to produce enough insulin or when the body cannot effectively use the insulin produced by such cells. Accordingly, early diagnosis will decrease the long-term effects and high-healthcare costs of diabetes.

objectiveThe objective is developing an integrated mathematical model of the insulin signaling network based on Brännmark's model, which can simulate the signaling events more comprehensively with the added key components.

methodsIn this study, a thorough mathematical model of the insulin signaling network was developed by expanding the previously validated model and incorporating the glycogen synthesis module. Parameters (69 parameters) of the integrated model were evaluated by a genetic algorithm by fitting the model predictions to eighty percent of experimental data from the literature. Twenty percent of the experimental data were used to evaluate the final optimized model.

resultsThe time-response curves indicate that the GS phosphorylation reaches its maximum in response to 10

conclusionConsiderably, the trends of all signaling components simulated by the expanded model shows high compatibility with experimental data (R2 ≥ 0.9), which approves the accuracy of the proposed model. The proposed mathematical model can be used in many biological systems and combined with the whole-body model of the blood glucose regulation system for a better understanding of the causes and potential treatment of type 2 diabetes. Although, this model is not a complete description of insulin signaling, yet it can make profound contributions to improvements regarding other important components and signaling branches such as epidermal growth factor (EGF) signaling, as well as signaling in other cell types in the model structure of future works.