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 alpha (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 alpha 1-isoform polypeptide (88% at 3 weeks, 94% at 8 weeks) after induction of diabetes by streptozotocin. Reductions in alpha 2 and alpha 3 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 alpha 1 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 alpha 1, much more than alpha 2 or alpha 3, catalytic subunit isoform of Na+,K(+)-ATPase in the pathogenesis of diabetic neuropathy.