Figure 5.

Mitochondrial oxidants induces selective insulin resistance. MitoPQ generates oxidants (O₂^˙̄ and H₂O₂; denoted by O₂^˙̄) in the mitochondrial matrix without impairing oxidative phosphorylation. Mitochondrial oxidants inhibit insulin-stimulated GLUT4 translocation and glucose uptake in adipocytes and myocytes, but AMPK-stimulated GLUT4 translocation is not impaired. MitoPQ did not impair insulin signaling to TBC1D4 or Akt-mediated activation of protein synthesis and inhibition of lipolysis, indicating that mitochondrial oxidants impair processes downstream of TBC1D4 phosphorylation in the insulin-regulated GLUT4 trafficking pathway.