To the Editor:
Drenger et al. have demonstrated that sevoflurane postconditioning is cancelled in the rat heart with type 1 diabetes mellitus and that this adverse effect by glucose intolerance cannot be restored by the adjustment of blood glucose using insulin.1This study appears to have many questions regarding the mechanisms of insulin's action, whereas we would congratulate their impressive results. In the study by Drenger et al. , the treatment with insulin significantly increased the infarct size in rats with diabetes mellitus, and a phosphatidylinositol-3-kinase inhibitor wartmannin demonstrated the effect to a similar extent.1As Drenger et al. have mentioned in the Discussion section, this phenomenon is difficult to explain1because insulin is a well-known phosphatidylinositol-3-kinase activator in the cardiac myocytes.2As a previous elegant study showed that diabetes abolishes the morphine-induced postconditioning effect in the rat heart, evaluation of the related pathways, including glycogen synthase kinase 3β, janus-activated kinase, signal transducer and activator of transcription 1, phosphatidylinositol-3-kinase/Akt, and extracellular signal-related kinase, in addition to signal transducer and activator of transcription 3, would help in understanding the study by Drenger et al. 1,3Diabetes mellitus may down-regulate a redox sensitive transcription factor, NF-E2-related factor 2 activity via extracellular signal-related kinase, resulting in impairment of the sevoflurane postconditioning effect because this pathway has been proved to be induced by the oxidative stress in the diabetic heart.2We also have to keep in mind that 5-hydroxydecanonate is not a selective inhibitor of mitochondrial adenosine triphosphate sensitive K+channels anymore because it is a substrate for the enzyme acyl-CoA synthethase in the electron transport chain of mitochondria,4and it is capable of playing a role as an inhibitor of sarcolemmal adenosine triphosphate sensitive K+channels.5Therefore, further studies are needed to clarify the mechanistic role of insulin in relation to diabetes mellitus on the sevoflurane postconditioning effect toward the ischemic heart.