Glucose-dependence of Renin-angiotensin system in podocytes cells during diabetic kidney disease
2017 SIAM Conference on Computational Science and Engineering
We have formulated a mathematical model that describes the glucose-sensitive reaction network that triggers the synthesis of ANG II. The local podocyte RAS signaling pathway is represented by a system of ordinary differential equations to track RAS peptides, enzymes, and receptors without explicit glucose-dependence. Glucose-dependence was added to the model through making the parameters functions of glucose. Literature experimental studies were used to estimate the unknown parameters and kinetic constants for the model under different glucose levels. The results showed a rise in ANG II levels with increasing glucose concentrations consistent with experimental observations. We were able to discriminate between possible models for the glucose dose-dependency of intracellular ANG II production in podocytes. The resulting model can be used to study the effect of different combinations of various ANG II modulating therapies such as ACE inhibitors, which could be useful for drug development.
- Minu Pilvankar, Oklahoma State University, USA, firstname.lastname@example.org