Advanced glycation end‐products impair Na + /K + ‐ ATP ase activity in diabetic cardiomyopathy: Role of the adenosine monophosphate‐activated protein kinase/sirtuin 1 pathway

Summary Decreased Na + /K + ‐ ATP ase activity, and both sirtuin 1 ( SIRT 1) and adenosine monophosphate‐activated protein kinase ( AMPK ) have been reported to be involved in the development of diabetic cardiomyopathy ( DCM ). The present study aimed to investigate the advanced glycation end‐products ( AGE ) that impair Na + /K + ‐ ATP ase stability by regulating the AMPK / SIRT 1 pathway during progression of DCM . To study type 1 diabetic mellitus (T1 DM ), a disease model in rats was established by a single intraperitoneal injection of streptozotocin ( STZ ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT 1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na + /K + ‐ ATP ase activity was also monitored. Using in vivo rat models of DCM , we showed that Na + /K + ‐ ATP ase activity decreased when both AMPK and SIRT 1 expression were downregulated. In vitro , AGE impaired Na + /K + ‐ ATP ase activity and decreased the AMPK and SIRT 1 expression. Sirtuin 1 overexpression increased Na + /K + ‐ ATP ase activity. 5‐aminoimidazole‐4‐carboxamide‐3‐ribonucleoside ( AICAR ) upregulated SIRT 1 expression and increased Na + /K + ‐ ATP ase activity, which could be partially abolished by splitomicin. Our results suggest that the dysfunction of DCM is related to AGE ‐induced Na + /K + ‐ ATP ase activity impairment through a mechanism involving the AMPK / SIRT 1 pathway.