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

SIMPLE SUMMARY: We investigated sodium–potassium pump (Na,K-ATPase) activity and oxidative stress markers in kidney samples of obese Zucker diabetic fatty (ZDF) rats to characterize this animal model of type 2 diabetes mellitus (T2DM) more thoroughly. Two controls—lean ZDF counterparts and Wistar rats—were used. We hypothesized that renal parameters depend on T2DM severity, as well as on the applied control. Our results suggest that the similar genetic background of obese and lean ZDF rats makes lean ZDF controls predisposed to abnormalities observed in obese counterparts. Obese ZDF rats with well-developed T2DM showed higher lipid peroxidation in the renal medulla and a higher ability of Na,K-ATPase to utilize the energy substrate in comparison with obese ZDF rats with lower glycemia. 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, as the transport of Na(+) from the tubular cells is necessary for glucose reabsorption. PubMed database revealed more than 6000 results (August 2022) for the keyword “Zucker rat”, confirming their intense usage in research; therefore, a comprehensive characterization of this T2DM model is desirable. 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.