Regulatory networks and complex interactions between the insulin and angiotensin II signalling systems: models and implications for hypertension and diabetes

Abstract

The cross-talk between insulin and angiotensin II signalling pathways plays a significant role in the co-occurrence of diabetes and hypertension. We developed a mathematical model of the system of interactions among the biomolecules that are involved in the cross-talk between the insulin and angiotensin II signalling pathways. We have identified several feedback structures that regulate the dynamic behavior of the individual signalling pathways and their interactions. Different scenarios are simulated and dominant steady-state, dynamic and stability characteristics are revealed. The proposed mechanistic model describes how angiotensin II inhibits the actions of insulin and impairs the insulin-mediated vasodilation. The model also predicts that poor glycaemic control induced by diabetes contributes to hypertension by activating the renin angiotensin aystem.