Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration

DS Skundric, RP Lisak - Journal of Diabetes Research, 2003 - hindawi.com
DS Skundric, RP Lisak
Journal of Diabetes Research, 2003hindawi.com
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 …
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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