Concurrent impairment of (Na++ K+)-ATPase activity in multi-organ of type-1 diabetic NOD mice

BackgroundType-1 diabetes causes serious complications. Detailed molecular pathways of type-1 diabetes-mediated organ dysfunction are not completely understood. Significantly depressed (Na++ K+)-ATPase (NKA) activity has been found in erythrocytes, pancreatic β-cells, nerve cells, and muscle tissues of type-1 diabetic patients and rodent animal models. The characteristics of NKA in the development of the type-1 diabetes-mediated complications remain obscure. Here we investigated whether alterations of NKA activity in heart, kidney, and pancreas of type-1 diabetic mice occur simultaneously and whether depressed NKA activity is a universal phenomenon in major organs in the development of type-1 diabetes-induced complications.MethodsFemale non-obese diabetic (NOD) and non-obese resistant mice were used for the study. Mice blood glucose was monitored and ouabain-sensitive NKA activity was determined.ResultsExperimental results reveal that reduced NKA activity correlates with the progression of elevated blood glucose along with marked altered NKA apparent Na+ affinity in all three organs of NOD mice. No significant changes of NKA protein expression were detected while the enzyme activity was reduced in tested mice, suggesting an inactive form of NKA might present in different tissues of the NOD mice.ConclusionOur study suggests that concurrent impairment of NKA function in multi-organ may serve as one of the molecular pathways participating in and contributing to the mechanism of type-1 diabetes-induced complications in NOD mice. A successful protection of NKA function from injury might offer a good intervention for controlling the progression of the disease.