Glomerular Na⁺-K⁺-ATPase Activity in Acute and Chronic Diabetes and With Aldose Reductase Inhibition

Sorbitol accumulation, myo-inositol depletion, and reduced Na⁺-K⁺-ATPase activity have been identified in experimental diabetes in several tissues in which diabetic complications occur. However, a reduction in renal Na⁺-K⁺-ATPase activity has not been universally reported, prompting us to examine the influence of diabetes duration on the activity of this enzyme complex in isolated glomeruli. Additionally, we examined the ability of the aldose reductase inhibitor sorbinil to directly stimulate glomerular Na⁺-K⁺-ATPase activity in vitro, an area of interest in view of the central position that the ability of sorbinil to restore Na⁺-K⁺-ATPase activity in vivo occupies in the interpretive scheme that links associated changes in sorbitol, myo-inositol, and Na⁺-K⁺-ATPase to enhanced polyol-pathway activity. Glomerular Na⁺-K⁺-ATPase activity was significantly decreased in rats with acute (< 18 days) streptozocin-induced diabetes but was significantly > control values in rats with more chronic (> 32 days) diabetes. In vitro addition of sorbinil (1 × 10⁻⁷ M) directly stimulated Na⁺-K⁺-ATPase in control (0.627 ± 0.090 vs. 0.843 ± 0.098 μmol P_i · mg⁻¹ · min⁻¹) but not diabetic glomeruli. These results indicate that the time of examination after induction of diabetes critically influences glomerular Na⁺-K⁺-ATPase activity and suggest that sorbinil, at least in normal glomerular tissue, has a membrane-associated effect that may be independent of its aldose reductase–inhibiting property.