Ameliorative potential of conditioning on ischemia-reperfusion injury in diabetes

Diabetes is a serious metabolic disease characterized by hyperglycemia. Diabetes also leads to several long-term secondary complications. Cardiovascular disease is an important complication of diabetes and is a major contributor to morbidity and mortality in diabetic subjects. The discovery of conditioning-induced ischemic or anoxic tolerance has led to the demonstration of the protective potential of conditioning as a treatment strategy to mitigate ischemia-reperfusion injury. Diabetes modulates multiple metabolic pathways and signal transduction cascades. Some of these pathways may overlap with mechanisms that mediate the beneficial effects of conditioning from the body's reaction to a sublethal insult, indicating the possibility of a potential interaction between diabetes and conditioning. Studies demonstrate that diabetes abrogates the ameliorative effect of various forms of conditioning, such as ischemic preconditioning, ischemic postconditioning, remote ischemic conditioning and pharmacological conditioning, on ischemia-reperfusion injury in various animal models. Moreover, drugs used to treat diabetes may have a potential impact on protection afforded by conditioning from ischemic injury. Studies also indicate a potential impact of various anti-diabetic drugs on conditioning-induced protection. Overall, the literature suggests that a better understanding of the overlap among pathways activated by diabetes and those involved in induction of ischemia tolerance may help identify ideal conditioning paradigms to protect diabetic subjects from ischemic injury.