Isoform Specific Reductions in Na+,K+-ATPase Catalytic (α) Subunits in the Nerve of Rats with Streptozotocin-Induced Diabetes

Abstract: Na⁺,K⁺-ATPase activity in nerve is reduced in rats with streptozotocin-induced diabetes; three different isoforms of the α (catalytic) subunit of the enzyme are present in nerve. Using western blot to determine subunit isoform polypeptide levels in sciatic nerve, we found a substantial reduction in α1-isoform polypeptide (88% at 3 weeks, 94% at 8 weeks) after induction of diabetes by streptozotocin. Reductions in α2 and α3 polypeptide were smaller and not statistically significant. The reduction in amount of all three isoform polypeptides in the nerve of 3-week diabetic animals was corrected by administration of insulin. Accumulation of α1 polypeptide at a nerve ligature indicated that rapid transport of that polypeptide in nerve occurs with normal kinetics. The results implicate a specific marked deficit in α1, much more than α2 or α3, catalytic subunit isoform of Na⁺,K⁺-ATPase in the pathogenesis of diabetic neuropathy.