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The potential effects of anti-diabetic medications on myocardial ischemia–reperfusion injury

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Abstract

Heart disease and stroke account for 65% of the deaths in people with diabetes mellitus (DM). DM and hyperglycemia cause systemic inflammation, endothelial dysfunction, a hypercoagulable state with impaired fibrinolysis and increased platelet degranulation, and reduced coronary collateral blood flow. DM also interferes with myocardial protection afforded by preconditioning and postconditioning. Newer anti-diabetic agents should not only reduce serum glucose and HbA1c levels, but also improve cardiovascular outcomes. The older sulfonylurea agent, glyburide, abolishes the benefits of ischemic and pharmacologic preconditioning, but newer sulfonylurea agents, such as glimepiride, may not interfere with preconditioning. GLP-1 analogs and sitagliptin, an oral dipeptidyl peptidase IV inhibitor, limit myocardial infarct size in animal models by increasing intracellular cAMP levels and activating protein kinase A, whereas metformin protects the heart by activating AMP-activated protein kinase. Both thiazolidinediones (rosiglitazone and pioglitazone) limit infarct size in animal models. The protective effect of pioglitazone is dependent on downstream activation of cytosolic phospholipase A2 and cyclooxygenase-2 with subsequent increased production of 15-epi-lipoxin A4, prostacyclin and 15-d-PGJ2. We conclude that agents used to treat DM have additional actions that have been shown to affect the ability of the heart to protect itself against ischemia–reperfusion injury in preclinical models. However, the effects of these agents in doses used in the clinical setting to minimize ischemia–reperfusion injury and to affect clinical outcomes in patients with DM have yet to be shown. The clinical implications as well as the mechanisms of protection should be further studied.

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Acknowledgments

Some of the work performed by Y.Y., J.R.P.P., and Y.B was funded by research grants from Pfizer, Takeda, Merck, and Novartis.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA

    Yumei Ye, Jose R. Perez-Polo & Yochai Birnbaum

  2. Section of Cardiology, Department of Medicine, Baylor College of Medicine, 1709 Dryden Road, Suite 9.32 BCM 620, Houston, TX, 77030, USA

    David Aguilar & Yochai Birnbaum

  3. Texas Heart Institute, St Luke’s Episcopal Hospital, Houston, TX, USA

    Yochai Birnbaum

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  1. Yumei Ye
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  2. Jose R. Perez-Polo
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Correspondence to Yochai Birnbaum.

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Ye, Y., Perez-Polo, J.R., Aguilar, D. et al. The potential effects of anti-diabetic medications on myocardial ischemia–reperfusion injury. Basic Res Cardiol 106, 925–952 (2011). https://doi.org/10.1007/s00395-011-0216-6

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  • DOI: https://doi.org/10.1007/s00395-011-0216-6

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