Figure 3. Pancreatic toxicity of PERK inhibition.
PERK inhibition by either genetic deletion or pharmacological inhibition causes IFN signaling increase in pancreas and accumulation of misfolded insulin, proinsulin and glucose transporters Glut2, leading to hyperglycermia and diabetes. In human, PERK inactivation mutation results in Wlocott-Rallison syndrome, which is characterized with pancreatic degeneration and diabetes.