Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.
Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.
['Huang|Kai-Yu|KY|', 'Que|Jia-Qun|JQ|', 'Hu|Ze-Song|ZS|', 'Yu|Yong-Wei|YW|', 'Zhou|Ying-Ying|YY|', 'Wang|Lei|L|', 'Xue|Yang-Jing|YJ|', 'Ji|Kang-Ting|KT|', 'Zhang|Xin-Min|XM|']
D000818:Animals D017209:Apoptosis D001343:Autophagy D004353:Drug Evaluation, Preclinical D007004:Hypoglycemic Agents D007249:Inflammation D008297:Male D008687:Metformin D008810:Mice, Inbred C57BL D015428:Myocardial Reperfusion Injury D051057:Proto-Oncogene Proteins c-akt
Metformin inflammation apoptosis autophagy myocardial ischemia reperfusion