Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction

► We tested if XNT, an ACE2 activator, would improve diabetes-induced heart dysfunction. ► Diabetic rats showed heart dysfunction/hypertrophy/fibrosis which were blunted by XNT. ► ACE2 activation also increased cardiac ACE2/ACE ratio and decreased AT1 expression. ► Inhibition of ERK and modulation of AMPK-α and β1 are also involved in these effects. ► Activation of intrinsic ACE2 protects the heart against diabetes-induced dysfunction.