Metallothionein protection against streptozotocin-induced pancreatic beta cell damage and diabetes

Reactive oxygen species (ROS) have been proposed for a long time as one of the mechanisms for beta cell destruction in diabetes. Compared to other cell types pancreatic beta cells are much more vulnerable to the damage caused by ROS. This vulnerability is probably because beta cells contain very low levels of antioxidants that scavenger ROS. A striking example of beta-cell susceptibility is the severe damage done by streptozotocin (STZ). STZ is widely used to induce diabetes in experimental animals. It generates ROS and specifically attacks pancreatic beta cells with a destructive cascade, consisting of DNA damage, excess activation of the DNA repair enzyme poly (ADP-ribose) polymerase, and depletion of cellular NAD+. Metallothionein (MT) is an inducible antioxidant protein that has been shown to protect DNA from chemical damage in several cell types. Therefore we hypothesize that the deficiency in ROS detoxifying systems of beta cells results in beta cell vulnerability and enhanced ROS protection such as overexpression of MT will protect from beta cell death and diabetes. (Abstract shortened by UMI.)...