title: Mechanisms of diabetic neuropathy: Schwann cells.
abstract: As ensheathing and secretory cells, Schwann cells are a ubiquitous and vital component of the endoneurial microenvironment of peripheral nerves. The interdependence of axons and their ensheathing Schwann cells predisposes each to the impact of injury in the other. Further, the dependence of the blood-nerve interface on trophic support from Schwann cells during development, adulthood, and after injury suggests these glial cells promote the structural and functional integrity of nerve trunks. Here, the developmental origin, injury-induced changes, and mature myelinating and nonmyelinating phenotypes of Schwann cells are reviewed prior to a description of nerve fiber pathology and consideration of pathogenic mechanisms in human and experimental diabetic neuropathy. A fundamental role for aldose-reductase-containing Schwann cells in the pathogenesis of diabetic neuropathy, as well as the interrelationship of pathogenic mechanisms, is indicated by the sensitivity of hyperglycemia-induced biochemical alterations, such as polyol pathway flux, formation of reactive oxygen species, generation of advanced glycosylation end products (AGEs) and deficient neurotrophic support, to blocking polyol pathway flux.
authors.affiliation: Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: amizisin@ucsd.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mizisin
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000453:epidemiology; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology; D012583:Schwann Cells / Q000473:pathology*
keywords: Schwann cell; diabetic nerve injury; endoneurial microenvironment; myelinated and unmyelinated fibers; pathogenic mechanisms