Increased Renal Metabolism in Diabetes: Mechanism and Functional Implications

Abstract

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 Na⁺ reabsorption, NKA-dependent O₂ consumption (QO₂), 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 QO₂ as well as QO₂ in cortical tissue, which consists mainly of proximal tubular cells, was significantly higher in diabetic than in control rats. The increase in tissue QO₂ was entirely caused by increased NKA-dependent QO₂. 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, Na⁺ reabsorption, and QO₂, as well as the increase in RBF and GFR in diabetic rats. We conclude that diabetes is associated with increased renal O₂ 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.