Figure 4
Effect of feedback and crosstalk perturbation in the network. (i) Knock out AKTp positive feedback on IRS. The response remains non-anabolic and monostable for glucose levels up to 2 folds. At point ‘I’ glucose = 1.5 folds and Ps = 0.44; corresponding network diagram is shown in Figure S9. (ii) Knock out of Calcium positive feedback on cAMP. Catabolic response is weakening slightly at subnormal glucose levels such that it becomes homeostatic at glucose = 0.9 fold (at ‘J’ where Ps = 0.48; corresponding network diagram is shown in Figure S10). (C) Decoupling of AKTp crosstalk PDE3. This leads to inactivation of glucagon signalling module at subnormal glucose levels. (D) Decoupling of DAG crosstalk with PKC. This leads to inhibition of insulin signalling module at high glucose levels up to 2 folds. This shows that the effects of both crosstalk are mutually independent, with AKTp-PDE3 crosstalk playing role at subnormal glucose levels and DAG-PKC crosstalk playing role at high glucose levels.
