Type 2 diabetes progression: A regulatory network approach

In order to elucidate central elements underlying type 2 diabetes, we constructed a regulatory network model involving 37 components (molecules, receptors, processes, etc.) associated to signaling pathways of pancreatic beta-cells. In a first approximation, the network topology was described by Boolean rules whose interacting dynamics predicted stationary patterns broadly classified as health, metabolic syndrome, and diabetes stages. A subsequent approximation based on a continuous logic analysis allowed us to characterize the progression of the disease as transitions between these states associated to alterations of cell homeostasis due to exhaustion or exacerbation of specific regulatory signals. The method allowed the identification of key transcription factors involved in metabolic stress as essential for the progression of the disease. Integration of the present analysis with existent mathematical models designed to yield accurate account of experimental data in human or animal essays leads to reliable predictions for beta-cell mass, insulinemia, glycemia, and glycosylated hemoglobin in diabetic fatty rats.