AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy.
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TLDR
It is concluded that AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart by significantly enhances autophagic activity and preserves cardiac function in diabetic mice.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.read more
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Heart Failure in Type 2 Diabetes Mellitus.
Helena Kenny,E. Dale Abel +1 more
TL;DR: The state of knowledge about the impact of existing antihyperglycemic therapies on HF is summarized, potential mechanisms for beneficial or deleterious effects are discussed, and currently approved pharmacological therapies for HF are reviewed.
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Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes.
TL;DR: Dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis.
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Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy.
TL;DR: Understanding the complex interplay of oxidative/nitrosative stress with pro-inflammatory, metabolic and cell death pathways is critical to devise novel targeted therapies for diabetic cardiomyopathy, which will be overviewed in this brief synopsis.
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Emerging role of autophagy in kidney function, diseases and aging
Tobias B. Huber,Charles L. Edelstein,Björn Hartleben,Ken Inoki,Man Jiang,Daisuke Koya,Shinji Kume,Wilfred Lieberthal,Nicolas Pallet,Alejandro Quiroga,Kameswaran Ravichandran,Katalin Susztak,Sei Yoshida,Zheng Dong +13 more
TL;DR: Recent insights on the role of autophagy in kidney physiology and diseases are summarized alluding to possible novel intervention strategies for treating specific kidney disorders by modifying Autophagy.
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AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart
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TL;DR: How recent discoveries have extended and in some cases challenged existing paradigms, providing new insights into the regulation of AMPK, its diverse biological actions, and therapeutic potential in the heart is assessed.
References
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Journal ArticleDOI
Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice
Zhonglin Xie,Kai Lau,Bonnie Eby,Pedro Lozano,Chaoyong He,Becky Pennington,Hongliang Li,Shradha Rathi,Yunzhou Dong,Rong Tian,David C. Kem,Ming-Hui Zou +11 more
TL;DR: Investigating whether chronic activation of the AMP-activated protein kinase (AMPK) by metformin restores cardiac function and cardiomyocyte autophagy in OVE26 diabetic mice found that stimulation of AMPK may represent a novel approach to treat diabeticCardiomyopathy.