Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes

Streptozotocin (STZ) selectively destroys insulin-producing beta islet cell s of the pancreas providing a model of type I diabetes, Poly(ADP-ribose) po lymerase (PARP) is a nuclear enzyme whose overactivation by DNA strand brea ks depletes its substrate NAD(+) and then ATP, leading to cellular death fr om energy depletion. me demonstrate DNA damage and a major activation of PA RP in pancreatic islets of STZ-treated mice. These mice display a 500% incr ease in blood glucose and major pancreatic islet damage. In mice with homoz ygous targeted deletion of PARP (PARP -/-), blood glucose and pancreatic is let structure are normal, indicating virtually total protection from STZ di abetes. Partial protection occurs in PARP +/- animals. Thus, PARP activatio n may participate in the pathophysiology of type I diabetes, for which PARP inhibitors might afford therapeutic benefit.