Intracellular Na+ Concentration ([Na+]i) Is Elevated in Diabetic Hearts Due to Enhanced Na+–Glucose Cotransport

BackgroundIntracellular Na+ concentration ([Na+]i) regulates Ca2+ cycling, contractility, metabolism, and electrical stability of the heart. [Na+]i is elevated in heart failure, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na+]i is also increased in type 2 diabetes (T2D) due to enhanced activity of the Na+–glucose cotransporter. Methods and ResultsTo test this hypothesis, we used myocardial tissue from humans with T2D and a rat model of late‐onset T2D (HIP rat). Western blot analysis showed increased Na+–glucose cotransporter expression in failing hearts from T2D patients compared with nondiabetic persons (by 73±13%) and in HIP rat hearts versus wild‐type (WT) littermates (by 61±8%). [Na+]i was elevated in HIP rat myocytes both at rest (14.7±0.9 versus 11.4±0.7 mmol/L in WT) and during electrical stimulation (17.3±0.8 versus 15.0±0.7 mmol/L); however, the Na+/K+‐pump function was similar in HIP and WT cells, suggesting that higher [Na+]i is due to enhanced Na+ entry in diabet...