FIGURE 10.

The impact of the individual diabetes parameters. Shown are heat maps of the impact of the individual diabetes parameters on the measured model variables. Light color indicates a small contribution, and dark color indicates a large contribution. The mTORC1 feedback contributes to the reduction in the steady-state level of phosphorylation and to the increased EC₅₀ all over the insulin-signaling network. The reduction of IR levels also has slight effects network-wide, whereas all other diabetes parameters reflect peripheral protein levels, the reductions of which only have local effects. A, the contribution to the reduction in the steady-state level of phosphorylation for the diabetes parameters is calculated as the reduction from normal in the insulin-stimulated steady state for a single diabetes parameter (as indicated) divided by the reduction from normal in the diabetes simulation with all diabetes parameters. B, the contribution to the increase in EC₅₀ for the diabetes parameters is calculated as the increase above normal in EC₅₀ for a single diabetes parameter (as indicated) divided by the increase above normal in the diabetes simulation with all diabetes parameters.