INCREASED RENAL METABOLISM IN DIABETES MECHANISM AND FUNCTIONAL IMPLICATIONS

The coupling between the Na+/glucose cotransporter and Na+-K+-ATPase (NKA) described for epithelial cells (1) prompted us to study in rats with streptozocin-induced diabetes the effect of increased tubular glucose load on tubular Naf reabsorption, NKA-dependent O-2 consumption (QO(2)), and NKA activity. Filtered glucose is mainly reabsorbed in the proximal tubuli via the phlorizin-sensitive Na+/glucose cotransporter. In this study, the diabetic rats had a significantly higher renal blood flow (RBF), glomerular filtration rate (GFR), and Na+ reabsorption than the control rats. Total renal and QO(2) a as QO(2) in cortical tissue, which consists mainly of proximal tubular cells, was significantly higher in diabetic than in control rats. The increase in tissue and QO(2) wrely caused by increased NKA-dependent and QO(2). NKA activity, measured as rate of ATP hydrolysis, was increased in cortical tubular but not glomerular tissue from diabetic rats. Phlorizin treatment abolished the increase in NKA activity, Nat reabsorption, and and QO(2) as well as the increase in RBF and GFR in diabetic rats. We conclude that diabetes is associated with increased renal O-2, metabolism secondary to the increase in coupled Na+ reabsorption via the Na+/glucose cotransporter and NKA. The increased oxygen consumption might contribute to the hyperperfusion and hyperfiltration in the diabetic kidney.