Renal ouabain inhibitable Na-K ATPase activity and myoinositol supplementation in experimental diabetes mellitus.
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.
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy / Q000201:enzymology*; D005527:Food, Fortified; D007294:Inositol / Q000378:metabolism* / Q000627:therapeutic use; D007668:Kidney / Q000201:enzymology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D007294:Inositol; D010042:Ouabain; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D000254:Sodium-Potassium-Exchanging ATPase