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1575229 
Journal Article 
The potential effects of anti-diabetic medications on myocardial ischemia-reperfusion injury 
Ye, Y; Perez-Polo, JR; Aguilar, D; Birnbaum, Y 
2011 
Yes 
Basic Research in Cardiology
ISSN: 0300-8428
EISSN: 1435-1803 
106 
6 
925-952 
21892746 
WOS:000297708200003 
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 A(2) and cyclooxygenase-2 with subsequent increased production of 15-epi-lipoxin A
(4), prostacyclin and 15-d-PGJ(2). 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. 
Ischemia reperfusion injury; Infarct size; Type-2 diabetes mellitus; Anti-diabetic agents; Animal models