Controversies on the sensitivity of the diabetic heart to ischemic injury: the sensitivity of the diabetic heart to ischemic injury is decreased.
Controversy exists as to whether the diabetic heart is more or less sensitive to ischemic injury. Although a considerable number of experimental studies have directly determined the effects of ischemia on the diabetic heart, there is still no general agreement as to whether metabolic changes within the myocardium contribute to the severity of ischemic injury. This paper reviews the evidence suggesting that the diabetic heart can actually be less sensitive to an episode of severe ischemia. Possible reasons for this decreased sensitivity to injury are discussed, which include a decreased accumulation of glycolytic products during ischemia (lactate and protons), as well as alterations in the regulation of intracellular pH in the diabetic heart. Based on existing studies, we suggest that although impaired glucose metabolism in the diabetic heart contributes to injury in hypoxic hearts or in hearts subjected to low-flow ischemia, diabetes-induced decreases in glycolysis can actually be beneficial to the diabetic heart during and following a severe ischemic episode. A decreased clearance of protons via the Na+/H+ exchanger may also contribute to the decreased sensitivity to ischemic injury in the diabetic heart.
Feuvray
D
D
Laboratoire de Physiologie Cellulaire, Université Paris, Orsay, France.
Lopaschuk
G D
GD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D017923:Sodium-Hydrogen Exchangers; D005947:Glucose; D002118:Calcium