Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Abstract

For a better insight into relations between type 2 diabetes mellitus (T2DM) and Na,K-ATPase properties in kidneys, we aimed to characterize two subgroups of ZDF obese (fa/fa) rats, with more and less developed T2DM, and compare them with two controls: lean (fa/+) and Wistar. Na,K-ATPase enzyme kinetics were estimated by measuring the ATP hydrolysis in the range of NaCl and ATP levels. As Na,K-ATPase is sensitive to oxidative stress, we evaluated selected oxidative stress parameters in kidney homogenates. Our results suggest that thiol–disulfide redox balance in the renal medulla and Na,K-ATPase properties in the renal cortex differ between both controls, while observed measurements in lean (fa/+) rats showed deviation towards the values observed in ZDF (fa/fa) rats. In comparison with both controls, Na,K-ATPase enzyme activity was higher in the renal cortex of ZDF rats independent of diabetes severity. This might be a consequence of increased glucose load in tubular fluid. The increase in lipid peroxidation observed in the renal cortex of ZDF rats was not associated with Na,K-ATPase activity impairment. Regarding the differences between subgroups of ZDF animals, well-developed T2DM (glycemia higher than 10 mmol/L) was associated with a higher ability of Na,K-ATPase to utilize the ATP energy substrate.

Keywords

• type 2 diabetes mellitus
• kidney
• ZDF rats
• fa/fa
• fa/+
• sodium pump