RAC1 and Hyperinsulinemia: During hyperinsulinemia, aberrant phosphorylation of Ras-related C3 botulinum toxin substrate 1 (Rac1) by PI3K instead of its canonical target phosphatidylinositol 4,5-bisphosphate (PIP2) also leads to NOX-4 activation and ROS release in adipocytes [253].