Reaction Network Analysis of Metabolic Insulin Signaling

TL;DR

This paper applies advanced reaction network theory to analyze the insulin signaling system, revealing properties like concordance and absolute concentration robustness, and providing methods to determine equilibria and stability of key species.

Contribution

It extends reaction network analysis to insulin signaling, identifying concordance, ACR properties, and stable equilibria in a complex biological network.

Findings

The network is concordant, implying at most one positive equilibrium per class.

ACR is present in 8 species, including GLUT4, indicating robustness.

The method determines positive equilibria using deficiency-oriented coarsening.

Abstract

Absolute concentration robustness (ACR) and concordance are novel concepts in the theory of robustness and stability within Chemical Reaction Network Theory. In this paper, we have extended Shinar and Feinberg's reaction network analysis approach to the insulin signaling system based on recent advances in decomposing reaction networks. We have shown that the network with 20 species, 35 complexes, and 35 reactions is concordant, implying at most one positive equilibrium in each of its stoichiometric compatibility class. We have obtained the system's finest independent decomposition consisting of 10 subnetworks, a coarsening of which reveals three subnetworks which are not only functionally but also structurally important. Utilizing the network's deficiency-oriented coarsening, we have developed a method to determine positive equilibria for the entire network. Our analysis has also shown that the system has ACR in 8 species all coming from a deficiency zero subnetwork. Interestingly, we have shown that, for a set of rate constants, the insulin-regulated glucose transporter GLUT4 (important in glucose energy metabolism), has stable ACR.