REN and diabetes mellitus: The main findings of these experiments were as follows: (1) int-renin was involved in ischemic resistance in DM hearts, (2) DM hearts exhibited activated ERK1/2 during ischemia both in the whole cell and mitochondrial fractions, (3) r-renin activated mitochondrial ERK1/2, hyperpolarized ΔΨm, and inhibited atractyloside-induced mPTP opening in DM hearts, and (4) pharmacological inhibition of ERK1/2 by U0126 attenuated the ischemic resistance in DM hearts.