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Autophagy. 2011 Oct;7(10):1254-5. doi: 10.4161/auto.7.10.16740. Epub 2011 Oct 1.

AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy.

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  • 1Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. zxie@ouhsc.edu

Abstract

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.

PMID:
21685727
[PubMed - indexed for MEDLINE]
PMCID:
PMC3210311
Free PMC Article
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