Autophagy in insulin-induced hypoglycaemic neuropathy

Aim: Autophagy in neurons has been linked to a growing number of pathological conditions in the CNS, but the role of this process in peripheral neuropathy has received little attention. This study aimed to determine whether autophagy is involved in development of peripheral neuropathy in hypoglycaemic diabetic rats. Methods: The lateral plantar nerves, ventral roots, and dorsal roots of insulin-treated diabetic hypoglycaemic rats were examined for structural signs of autophagy by electron microscopy. Results: Autophagy-associated vacuoles were found in myelinated axons exhibiting early pathological changes but not in the associated Schwann cells. When the damaged axons degenerated, their associated Schwann cells gradually died and were cleared from the endoneurium by macrophages. During axonal regeneration, extensive signs of autophagy-related structures such as autophagophores appeared in regenerating axons and in the cytoplasm of the associated Schwann cells in the Band of Bungner. Conclusion: Autophagy occurs in hypoglycaemic peripheral nerves in association with axonal de- and regeneration. The extensive signs of autophagy in regenerated axons suggest that autophagy may play a role in survival of the new axons.