Axo-glial dysjunction. A novel structural lesion that accounts for poorly reversible slowing of nerve conduction in the spontaneously diabetic bio-breeding rat

J Clin Invest. 1986 Feb;77(2):474-84. doi: 10.1172/JCI112326.


Biochemical abnormalities in peripheral nerve are thought to precede and condition the development of diabetic neuropathy, but metabolic intervention in chronic diabetic neuropathy produces only limited acute clinical response. The residual, metabolically unresponsive neurological deficits have never been rigorously defined in terms of either persistent metabolic derangements or irreversible structural defects because human nerve tissue is rarely accessible for anatomical and biochemical study and experimentally diabetic animals do not develop the structural hallmarks of human diabetic neuropathy. Detailed neuroanatomical-functional-biochemical correlation was therefore undertaken in long-term spontaneously diabetic BB-Wistar rats that functionally and structurally model human diabetic neuropathy. Vigorous insulin replacement in chronically diabetic BB rats essentially normalized both the sural nerve fiber caliber spectrum and the decreased sciatic nerve myo-inositol and (Na,K)-ATPase levels generally associated with conduction slowing in diabetic animals; yet, nerve conduction was only partially restored toward normal. Morphometric analysis revealed a striking disappearance of paranodal axo-glial junctional complexes that was not corrected by insulin replacement. Loss of these strategic junctional complexes, which are thought to limit lateral migration of axolemmal Na channels away from nodes of Ranvier, correlates with and can account for the diminished nodal Na permeability and resultant nodal conduction delay characteristic of chronic diabetic neuropathy in this animal model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / pathology*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology*
  • Electrophysiology
  • Inositol / metabolism
  • Insulin / therapeutic use
  • Male
  • Myelin Sheath / metabolism
  • Nerve Fibers, Myelinated / pathology*
  • Neural Conduction*
  • Rats
  • Rats, Inbred Strains
  • Sciatic Nerve / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sural Nerve / pathology


  • Insulin
  • Inositol
  • Sodium-Potassium-Exchanging ATPase