Figure 2.

Consequences of losing dynamic IR signaling in podocytes. (A) Hyperinsulinaemia, hyperglycaemia, free fatty acids, and inflammation are all factors associated with systemic insulin resistance, that have been shown to disrupt podocyte insulin signaling, via several different mechanisms (60); (B) these mechanisms include directly affecting IR expression, increased ubiquitination of IRS-1, regulation of several proteins involved in insulin signaling, including SHP-1, SHIP-2, PTEN, ultimately disrupting downstream signal transduction; (C) Dysregulated IR signaling (either loss of IR signaling or uncontrolled activation of selective signaling branches) has the potential to influence several inter-connected metabolic pathways in podocytes. These include ER stress responses (promoting apoptosis), mitochondrial signaling, Akt and mTOR signaling, glucose transport and the regulation of F-actin dynamics.