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Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

High glucose (HG)-induced cardiomyocytes (CMs) injury is a leading cause of diabetic cardiomyopathy with little treatment options. Irisin, a new myokine, which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), has aroused great attentions as an essential cardioprotective factor and glucose metabolism regulator but little was known on diabetic cardiomyopathy yet. Here, we aim to clarify the role of irisin in the HG-induced CMs injury. Neonatal Sprague-Dawley (SD) rat CMs were cultured in a normal or high glucose medium for 12, 24 and 48 h respectively before exposing to irisin. The apoptosis level was determined by Terminal-deoxynucleotidyl transferase mediated-dUTP Nick End Labeling (TUNEL) assay. Cell viability was measured with the conventional methylthiazolyl tetrazolium (MTT) assay. Moreover, reactive oxygen species (ROS) production was evaluated by dihydroethidium (DHE) staining. Inflammatory factors, namely TNF-ɑ, IL-6, IL-1β were determined by enzyme-linked immunosorbent assay (ELISA) kits. Furthermore, protein and mRNA expressions were measured by Western blot and qRT-PCR respectively. HG increases the apoptosis of CMs and activated the inflammatory responses and oxidative stress in CMs. Meanwhile, the mRNA and protein expressions of FNDC5 are decreased after HG exposure. Nevertheless, the increased apoptosis is alleviated by irisin treatment. Notably, irisn suppresses the inflammatory responses and oxidative stress in injured CMs. Mechanically, after administration of Compound C, AMPK inhibitor, these cardioprotective effects resulting from irisin are reversed. Irisin plays a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. 

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