Inhibition of Brain-Type Glycogen Phosphorylase Ameliorates High Glucose-Induced Cardiomyocyte Apoptosis Via Akt-HIF-1α Activation.

The brain-type glycogen phosphorylase (pygb) is one of the rate-limiting enzyme in glycogenolysis that plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Here we investigated the role of pygb in high glucose (HG)-induced cardiomyocyte apoptosis and explored the underlying mechanisms, by using the specific pygb inhibitors or pygb siRNA. Results showed that inhibition of pygb significantly attenuated cell apoptosis and oxidative stress induced by HG in H9c2 cardiomyocytes. Inhibition of pygb improved glucose metabolism in cardiacmyocytes, as evidenced by increased glycogen content, glucose consumption and glucose transport. Mechanismly, pygb inhibition activated Akt/GSK-3β signal pathway and suppressed NF-κB activation in H9c2 cells exposed to HG. Additionally, pygb inhibition promoted the expression and the translocation of hypoxia-inducible factor-1α (HIF-1α) after HG stimulation. However, the changes in glucose metabolism and HIF-1α activation mediated by pygb inhibition were significantly reversed in the presence of Akt inhibitor MK2206. In conclusion, the present study suggested that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via Akt-HIF-α activation.