We have recently shown that in diabetic OVE26 mice (type I diabetes), the 
AMP-activated protein kinase (AMPK) is reduced along with cardiac dysfunction 
and decreased cardiac autophagy. Genetic inhibition of AMPK in cardiomyocytes 
attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases 
mortality in diabetic mice. More importantly, we have found chronic AMPK 
activation with metformin, one of the most used antidiabetes drugs and a 
well-characterized AMPK activator, significantly enhances autophagic activity, 
preserves cardiac function and prevents most of the primary characteristics of 
diabetic cardiomyopathy in OVE26 mice, but not in dominant negative-AMPK 
diabetic mice. We conclude that AMPK activation protects cardiac structure and 
function by increasing cardiac autophagy in the diabetic heart.