Insulin receptor binding kinetics: modeling and simulation studies (Receptor Aggregation Model)

Model Status

This CellML model runs in both OpenCell and COR and represents the receptor aggregation model from the original published paper (equations 8-16). The units have been checked and they are consistent. In the absence of published initial conditions for x1-x9 arbitary values have been used. The simulation output from this model does not match the published paper.

Model Structure

ABSTRACT: Biological actions of insulin regulate glucose metabolism and other essential physiological functions. Binding of insulin to its cell surface receptor initiates signal transduction pathways that mediate cellular responses. Thus, it is of great interest to understand the mechanisms underlying insulin receptor binding kinetics. Interestingly, negative cooperative interactions are observed at high insulin concentrations while positive cooperativity may be present at low insulin concentrations. Clearly, insulin receptor binding kinetics cannot be simply explained by a classical bimolecular reaction. Mature insulin receptors have a dimeric structure capable of binding two molecules of insulin. The binding affinity of the receptor for the second insulin molecule is significantly lower than for the first bound insulin molecule. In addition, insulin receptor aggregation occurs in response to ligand binding and aggregation may also influence binding kinetics. In this study, we develop a mathematical model for insulin receptor binding kinetics that explicitly represents the divalent nature of the insulin receptor and incorporates receptor aggregation into the kinetic model. Model parameters are based upon published data where available. Computer simulations with our model are capable of reproducing both negative and positive cooperativity at the appropriate insulin concentrations. This model may be a useful tool for helping to understand the mechanisms underlying insulin receptor binding and the coupling of receptor binding to downstream signaling events.

The original paper reference is cited below:

Insulin receptor binding kinetics: modeling and simulation studies, Sumanas Wanant and Michael J. Quon, 2000, Journal of Theoretical Biology, 205, 355-364. PubMed ID: 10882558

A schematic diagram of Wanant and Quon's 2000 receptor aggregation model.