Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening

Background In the majority of studies, metformin has been demonstrated to cardioprotect diabetic patients, the mechanism of which is unclear. We hypothesized that metformin cardioprotects the ischemic heart through the Akt-mediated inhibition of mitochondrial permeability transition pore (mPTP) opening. Materials and methods Isolated perfused hearts from normoglycemic Wistar or from diabetic Goto-Kakizaki (GK) rats ( N ≥ 6/group) were subjected to 35 min ischemia and 120 min of reperfusion. Metformin (50 µmol/l) was added for 15 min at reperfusion, alone or with LY294002 (15 µmol/l), a PI3K inhibitor. Infarct size and Akt phosphorylation were measured. Furthermore, the effect of metformin on mPTP opening in adult cardiomyocytes isolated from both strains was determined. Results Metformin reduced infarct size in both Wistar (35 ± 2.7% metformin vs. 62 ± 3.0% control: P