When isolated hearts were perfused with U0126, where cytosolic and mitochondrial ERK1/2 were significantly suppressed both in non-DM and DM hearts (Figure 4e,f), U0126 abolished ischemic resistance of DM hearts; i.e., U0126 decreased LVDP (DM hearts with U0126; 96.4 ± 3.2 mmHg, p < 0.05 vs. 112.7 ± 3.1 mmHg of DM hearts, Figure 4c) and increased LVEDP during ischemia in DM hearts (DM hearts with U0126; 18.3 ± 4 mmHg p < 0.05 vs. 10.3 ± 0.7 mmHg of DM, Figure 4d), whereas did not alter in non-DM hearts (Figure 4a,b). This evidence concerns the gene MAPK3 and ischemia.