A mathematical model of metabolic insulin signaling pathways based on the work of Ahmad Sedaghat, Arthur Sherman and Michael Quon [2002, AM J Physiol Endocrinol Metab, 283,E1084-E1101].

Description

    This is a mathematical model that explicitly represents many of the known 
    signaling components mediating translocation of the insulin-responsive glucose 
    transporter GLUT4 and gives insight into the complexities of metabolic insulin 
    signaling pathways. A novel mechanistic model of postreceptor events including 
    phosphorylation of insulin receptor substrate-1,activation of phosphatidylinositol 
    3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C 
    is coupled with previously validated subsystem models of insulin receptor binding, 
    receptor recycling, and GLUT4 translocation. A system of differential equations is 
    defined by the structure of the model. Rate constants and model parameters are 
    constrained by published experimental data. Model simulations of insulin 
    dose-response experiments agree with published experimental data and also generate 
    expected qualitative behaviors such as sequential signal amplification and increased 
    sensitivity of downstream components.

    This JSim version was developed by Maris Lemba [2003] as a project while at the University of Washington.

Figure 1: Diagram of model with feedback. From Sedaghat et al. 2002 paper.

Figure 2: No feedback. Figure 6 from Sedaghat et al. 2002 paper. Time course for (Top) unbounded receptors (Rp), once and twice-bound phosphorylated surface receptors (RIPp and RI2p),(bottom) total phosphorylated surface receptors (RI2p+RIPp), and unphosphorylated (IRS1) and tyrosine-phosphorylated IRS-1 after a step input of insulin fo 15 min. Purple dashed line is insulin input pulse.

Equations

The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.