Insulin ve angiotensin sistemlerinin karmaşık ilişkileri: Hipertansiyon ve diyabete etkileri

Clinical evidence shows that there is a correlation between diabetes and hypertension diseases. This thesis applies the tools of systems biology 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 signaling pathways. AKT, also known as Protein Kinase B, plays a key regulatory role in metabolic actions of insulin. While being a significant factor in pathophysiology of hypertension, Ang II also induces insulin resistance. We developed dynamic models of the system of interactions among the biomolecules that play important roles in cross-talk between the insulin and Ang II signaling pathways. Embedded feedback structures are revealed. Different scenarios are simulated and dominant dynamic characteristics are investigated. We showed that Ang II inhibits the actions of insulin by interfering with Insulin-AKT signaling reducing insulin-mediated glucose uptake and impairing insulin-mediated vasodilation. Also diabetic state, defined by the poor glucose control, contributes to the progression of hypertension by inducing hyperglycemia. This model provides insight into the complexity of cellular networks governing the development of diseases and hopefully paves the way for proposing targets for therapeutic interventions.