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Correspondence  |   February 2012
The Effect of Insulin May Not Be So Simple
Author Affiliations & Notes
  • Hiroyuki Kinoshita, M.D., Ph.D.
    *
  • *Wakayama Medical University, Wakayama, Japan. ;
Article Information
Correspondence
Correspondence   |   February 2012
The Effect of Insulin May Not Be So Simple
Anesthesiology 2 2012, Vol.116, 488. doi:10.1097/ALN.0b013e31823fd04d
Anesthesiology 2 2012, Vol.116, 488. doi:10.1097/ALN.0b013e31823fd04d
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.1 This 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.1 As Drenger et al.  have mentioned in the Discussion section, this phenomenon is difficult to explain1 because insulin is a well-known phosphatidylinositol-3-kinase activator in the cardiac myocytes.2 As 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.  1,3 Diabetes 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.2 We 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,4 and it is capable of playing a role as an inhibitor of sarcolemmal adenosine triphosphate sensitive K+channels.5 Therefore, 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.
References
Drenger B, Ostrovsky IA, Barak M, Nechemia-Arbely Y, Ziv E, Axelrod JH: Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: Phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition. ANESTHESIOLOGY 2011; 114:1364–72
Tan Y, Ichikawa T, Li J, Si Q, Yang H, Chen X, Goldblatt CS, Meyer CJ, Li X, Cai L, Cui T: Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes 2011; 61:625–33
Gross ER, Hsu AK, Gross GJ: Diabetes abolishes morphine-induced cardioprotection via multiple pathways upstream of glycogen synthase kinase-3beta. Diabetes 2007; 56:127–36
Hanley PJ, Mickel M, Löffler M, Brandt U, Daut J: K(ATP) channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart. J Physiol 2002; 542:735–41
Li X, Rapedius M, Baukrowitz T, Liu GX, Srivastava DK, Daut J, Hanley PJ: 5-Hydroxydecanoate and coenzyme A are inhibitors of native sarcolemmal KATP channels in inside-out patches. Biochim Biophys Acta 2010; 1800:385–91