Fig. 7.

Architecture of a signaling network that accounts for the relation between the effects of insulin, ATIC, and ATP level. Insulin inputs in a double incoherent mode: IR autophosphorylation plus PTPLAD1 recruitment at the cell surface (1) are converted into robust oscillations in output through the overlay of two positive feedback systems with delay driven by the metabolic enzyme ATIC (2). A local interacting loop counteracting the action of PTPLAD1 (3). Adenylates production. Variations in ATIC levels or in adenylates synthesis or a decline in ATP levels independent of de novo purine biosynthesis increase the AMPK activity and IR endocytosis.