AGER and diabetes mellitus: In addition, RAGE-null mice with diabetes have been previously demonstrated to be significantly protected against the adverse impact of ischemia/reperfusion (I/R) injury of the heart, and key markers of apoptosis, including caspase-3 activity and cytochrome c release, were found to be decreased in the hearts of RAGE-null mice with diabetes compared with those in wild-type mice with diabetes during myocardial I/R (11).