Role of Neuropoietic Cytokines in Development and Progression of Diabetic Polyneuropathy: From Glucose
Metabolism to Neurodegeneration |
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Authors: | Dusanka S Skundric Robert P Lisak |
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Institution: | 1. Department of Neurology, Division of Neuroimmunology and Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit Medical Centre, 421 E. Canfield, 3141 Elliman Building, Detroit, Michigan, 48201, USA, |
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Abstract: | Diabetic neuropathy develops as a result of hyperglycemia-
induced local metabolic and microvascular
changes in both type I and type II diabetes mellitus. Diabetic
neuropathy shows slower impulse conduction, axonal degeneration,
and impaired regeneration. Diabetic neuropathy
affects peripheral, central, and visceral sensorimotor
and motor nerves, causing improper locomotor and visceral
organ dysfunctions. The pathogenesis of diabetic neuropathy
is complex and involves multiple pathways. Lack
of success in preventing neuropathy, even with successful
treatment of hyperglycemia, suggests the presence of early
mediators between hyperglycemia-induced metabolic and
enzymatic changes and functional and structural properties
of Schwann cells (SCs) and axons. It is feasible that
once activated, such mediators can act independently of the
initial metabolic stimulus to modulate SC-axonal communication.
Neuropoietic cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), leukemia inhibitory factor (LIF),
ciliary neurotrophic factor (CNTF), tumor necrosis factor
alpha (TNF-α), and transforming growth factor beta (TGF-
β), exhibit pleiotrophic effects on homeostasis of glia and
neurons in central, peripheral, and autonomic nervous system.
These cytokines are produced locally by resident and
infiltrating macrophages, lymphocytes, mast cells, SCs, fibroblasts,
and sensory neurons. Metabolic changes induced
by hyperglycemia lead to dysregulation of cytokine control.
Moreover, their regulatory roles in nerve degeneration and regeneration may potentially be utilized for the prevention
and/or therapy of diabetic neuropathy. |
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