Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS– Mediated Signaling

OBJECTIVE—Clinical studies have reported that metformin reduces cardiovascular end points of type 2 diabetic subjects by actions that cannot solely be attributed to glucose-lowering effects. The therapeutic effects of metformin have been reported to be mediated by its activation of AMP-activated protein kinase (AMPK), a metabolite sensing protein kinase whose activation following myocardial ischemia has been suggested to be an endogenous protective signaling mechanism. We investigated the potential cardioprotective effects of a single, low-dose metformin treatment (i.e., 286-fold less than the maximum antihyperglyce-mic dose) in a murine model of myocardial ischemia-reperfusion (I/R) injury. RESEARCH DESIGN AND METHODS—Nondiabetic and dia-betic (db/db) mice were subjected to transient myocardial isch-emia for a period of 30 min followed by reperfusion. Metformi