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Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session III Abstracts
Modeling and Dynamic Analysis of Feedback Loops of the Insulin and Angiotensin II
Signalling Systems
Yaman Arkun
1
, Deniz Cizmeci
2
.
1
Koc University, Istanbul, Turkey,
2
University of Exeter, Exeter, United Kingdom
This work applies the tools of systems theory to analyze the structure and the dynamics of the
complex cellular networks associated with diabetes and hypertension. The primary research
focus is the interaction between Angiotensin II (Ang II) and Insulin AKT signalling pathways.
We provide a better understanding of design and operating principles of processes such as
glucose uptake, cell proliferation, and blood pressure control by developing mathematical
models of interactions at the system level. The overall model is a dynamic nonlinear model that
includes mass-action kinetics and conservation laws. System behavior is analyzed within the
context of signalling pathways and feedback regulation. We show that complex signalling
pathways that govern the cross-talk between hypertension and diabetes are regulated by a nested
set of feedback loops that are organized in hierarchical fashion. Using the dynamic models we
develop, we simulate different scenarios to elucidate the functions of these feedback structures.
While doing so, dominant steady-state and dynamic characteristics that determine the normal and
diseased states are revealed. In particular parametric sensitivity and bistability of these feedback
loops are shown to affect the regulatory mechanisms such as glucose uptake and vasodilation-
vasoconstriction balance.
