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Alterations in ouabain inhibitable Na-K ATPase activity, polyol pathway activity, and myoinositol metabolism are part of a unifying hypothesis proposed to explain the pathogenesis of the chronic complications of diabetes mellitus. Direct measurements of renal ouabain inhibitable Na-K ATPase activity in animals with streptozotocin-induced diabetes show increased or decreased activity, depending on the nephron segment examined and the duration of diabetes. While myoinositol feeding corrects depressed Na-K ATPase activity in peripheral nerve of streptozotocin diabetic rats, the effect of myoinositol feeding on altered renal Na-K ATPase activity is unknown. To assess the effect of experimental diabetes on renal ouabain inhibitable Na-K ATPase activity and test the involvement of the polyol/inositol pathway, we assayed kidneys from normal, streptozotocin diabetic, and myoinositol-supplemented diabetic rats for renal ouabain-inhibitable Na-K ATPase, alkaline phosphatase, and tau-glutamyltranspeptidase (tau-GT) activity. Ouabain inhibitable Na-K ATPase activity, expressed per milligram of protein, is increased in the inner medulla of the diabetic kidney compared with normal and, expressed per microgram DNA, is increased in both the inner medulla and cortex. Myoinositol supplementation did not affect the increase in renal enzyme activity seen with streptozotocin diabetes. These observations suggest that the regulation of renal ouabain inhibitable Na-K ATPase activity, in streptozotocin diabetes, does not depend on supplemental myoinositol. These findings do not exclude the possibility that changes in polyol or myoinositol concentrations in a specific nephron segment may have pathogenetic significance for diabetic nephropathy.

Erythrocytes from normal adults with no personal or family history of bipolar affective disorder were analyzed by fluorescence spectroscopy to determine what effect, if any, acute in vitro incubation with lithium had on erythrocyte membrane dynamics. The effects on erythrocyte membrane molecular dynamics of varying concentrations of Li2CO3 (0.25-2.0 meq/liter), varying incubation temperatures (25-40 degrees C), and varying incubation times (5-185 min) were investigated. Following incubation with Li2CO3, the erythrocytes were labeled with either 4-phenylspiro-[furan-2(3H),--1'phthalan]--3,3'-dione (fluorescamine), which binds to membrane surface primary amines, or 12(9)anthroyl stearate [12(9)AS], which inserts deep in the membrane hydrocarbon core. The membrane molecular dynamics were then determined by fluorescence anisotropy measurements. These studies demonstrate that clinically relevant concentrations of Li+ incubated with intact normal human erythrocytes significantly alters molecular dynamics on the erythrocyte membrane surface, with less striking changes in the hydrocarbon core. A possible interpretation of these findings is that hydrated Li+ alters the electrostatic interaction of membrane surface molecules, as well as the surrounding solvent (water) structure, with a resultant increase in the molecular motion of these molecules. Alterations in membrane receptor motion could potentially alter receptor functional activity. If similar motional alterations were to occur in the interior of a membrane channel, such as an ionophore, the functional activity of the channel could also be potentially altered. These findings provide additional insight into possible biological actions of Li+, as well as potential molecular alterations in bipolar affective disorder erythrocytes.