Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Autophagy. 2011 Oct;7(10):1254-5. doi: 10.4161/auto.7.10.16740. Epub 2011 Oct 1.
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.
我们最近发现，在糖尿病 OVE26 小鼠（1 型糖尿病）中，AMP 激活的蛋白激酶（AMPK）的活性降低，伴随着心脏功能障碍和心脏自噬减少。在心肌细胞中遗传抑制 AMPK 会减弱心脏自噬，加重心脏功能障碍，并增加糖尿病小鼠的死亡率。更重要的是，我们发现用二甲双胍（最常用的抗糖尿病药物之一，也是一种经过充分研究的 AMPK 激活剂）慢性激活 AMPK 可显著增强自噬活性，保护心脏功能，并防止 OVE26 小鼠的大部分糖尿病心肌病的主要特征，但在显性负性 AMPK 糖尿病小鼠中则不然。我们得出结论，AMPK 的激活通过增加糖尿病心脏中的心脏自噬来保护心脏结构和功能。
