A myo-inositol–related defect in nerve Na+-K+-ATPase in experimental diabetes has been invoked in the pathogenesis of diabetic neuropathy, but the mechanism linking altered myo-inositol metabolism and Na+-K+-ATPase regulation in diabetic nerve is uncertain. Decreased Na+-K+-ATPase in diabetic rat nerve is normalized by aldose reductase inhibitors or dietary myo-inositol, which preserve normal nerve myo-inositol content in vivo. Decreased Na+-K+-ATPase in diabetic rabbit nerve is acutely reversed by exposure to protein kinase C agonists in vitro. This study explored the relationship between the myo-inositol–sensitive and protein kinase C–agonist–sensitive Na+-K+-ATPase defects in diabetic rat nerve. Ouabain-sensitive ATPase activity was measured in an enriched membrane fraction isolated from nondiabetic, streptozocin-induced diabetic, and myo-inositol–supplemented streptozocin-induced diabetic rats before and after the membranes were exposed to protein kinase C agonists in vitro. The decreased ouabain-sensitive ATPase activity in plasma membranes from untreated diabetic rats was increased after exposure to two structurally unrelated protein kinase C agonists; the normal ouabain-sensitive ATPase in plasma membranes from myo-inositol–supplemented diabetic rats was unaffected by protein kinase C agonists. The nonadditivity and implied equivalence of the Na+-K+-ATPase defect corrected by myo-inositol in vivo and by protein kinase C agonists in vitro are consistent with the postulated existence of a deficient myo-inositol–dependent phospholipid-derived protein kinase C agonist (presumably diacylglycerol) in diabetic nerve that regulates nerve Na+-K+-ATPase either directly or via a protein kinase C mechanism.
Normalization of Na+-K+-ATPase Activity in Isolated Membrane Fraction From Sciatic Nerves of Streptozocin-Induced Diabetic Rats by Dietary myo-Inositol Supplementation in Vivo or Protein Kinase C Agonists in Vitro
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Jean Kim, Harold Kyriazi, Douglas A Greene; Normalization of Na+-K+-ATPase Activity in Isolated Membrane Fraction From Sciatic Nerves of Streptozocin-Induced Diabetic Rats by Dietary myo-Inositol Supplementation in Vivo or Protein Kinase C Agonists in Vitro. Diabetes 1 May 1991; 40 (5): 558–567. https://doi.org/10.2337/diab.40.5.558
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