Role of Neuropoietic Cytokines in Development and Progression of Diabetic Polyneuropathy: From GlucoseMetabolism to Neurodegeneration

Skundric, Dusanka S; Lisak, Robert P.

doi:10.1155/edr.2003.303

Cited by 99 publications

(89 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Infl ammatory cytokines exhibit pleiotropic effects on glial cells and neurons. Cytokines regulate the process of degeneration and regeneration of peripheral nerves, which is essential in the pathogenesis of polyneuropathy [23]. Our results show that value of CRP is higher in patients with diabetic polyneuropathy in regard to patients without this complication and that is in accordance with results of other authors [24].…”

Section: Discussionsupporting

confidence: 92%

Markers of inflammation and microvascular complications in type 1 diabetes

et al. 2014

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 92%

Markers of inflammation and microvascular complications in type 1 diabetes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Cytokines and growth factors have been strongly implicated in the generation of pathological pain states at both peripheral and central nervous system sites (Lewin and Mendell 1993;Watkins et al, 1994) and in the development and progression of diabetic neuropathy (Skundric and Lisak 2003), although the role of cytokine transforming factors such as TGF-β . is unknown.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

View full text Add to dashboard Cite

The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-β isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/ group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-β1 and TGF-β2 mRNA, but not TGF-β3, was increased at 4 and 12 weeks. In sciatic nerve TGF-β3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-β formed homoand heterodimers, of which β 2 /β 3 , β 1 /β 1 , and β 1 /β 3 were significantly increased, while that of the TGF-β 2 /β 2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-β neutralizing antibody prevents the increase in total TGF-β protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-β2 > β1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-β neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-β isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-β neutralizing antibody. These findings implicate upregulation of TGF-β in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy.

show abstract

“…[105][106][107]111,112,114,124 Several reports indicate that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-␣) plays a role in nondiabetic painful neuropathy. [125][126][127] It is quite plausible that it also plays a role in diabetic neuropathic pain (as has been suggested 128,129 ), because TNF-␣ expression is increased in tissues of diabetic animals, and TNF-␣ induces overexpression of cyclooxygenase-2, 130,131 also implicated in diabetic hyperalgesia and allodynia. 97,99 TNF-␣ antagonists have never been tested in models of diabetic painful neuropathy.…”

Section: Strategies For Drug Discoverymentioning

confidence: 96%

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

2009

View full text Add to dashboard Cite

Summary:Advanced peripheral diabetic neuropathy (PDN) is associated with elevated vibration and thermal perception thresholds that progress to sensory loss and degeneration of all fiber types in peripheral nerve. A considerable proportion of diabetic patients also describe abnormal sensations such as paresthesias, allodynia, hyperalgesia, and spontaneous pain. One or several manifestations of abnormal sensation and pain are described in all the diabetic rat and mouse models studied so far (i.e., streptozotocin-diabetic rats and mice, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats, Zucker diabetic fatty rats, and nonobese diabetic, Akita, leptin-and leptin-receptor-deficient, and highfat diet-fed mice). Such manifestations are 1) thermal hyperalgesia, an equivalent of a clinical phenomenon described in early PDN; 2) thermal hypoalgesia, typically present in advanced PDN; 3) mechanical hyperalgesia, an equivalent of pain on pressure in early PDN; 4) mechanical hypoalgesia, an equivalent to the loss of sensitivity to mechanical noxious stimuli in advanced PDN; 5) tactile allodynia, a painful perception of a light touch; and 5) formalin-induced hyperalgesia. Rats with short-term diabetes develop painful neuropathy, whereas those with longer-term diabetes and diabetic mice typically display manifestations of both painful and insensate neuropathy, or insensate neuropathy only. Animal studies using pharmacological and genetic approaches revealed important roles of increased aldose reductase, protein kinase C, and poly(ADPribose) polymerase activities, advanced glycation end-products and their receptors, oxidative-nitrosative stress, growth factor imbalances, and C-peptide deficiency in both painful and insensate neuropathy. This review describes recent achievements in studying the pathogenesis of diabetic neuropathic pain and sensory disorders in diabetic animal models and developing potential pathogenetic treatments. Key Words: Animal models, diabetic insensate neuropathy, diabetic painful neuropathy, formalin-induced hyperalgesia, mechanical hyper-and hypoalgesia, pathogenetic treatments of diabetic neuropathic pain and sensory loss, symptomatic treatments of diabetic pain, tactile allodynia, thermal hyper-and hypoalgesia.

show abstract

Role of Neuropoietic Cytokines in Development and Progression of Diabetic Polyneuropathy: From GlucoseMetabolism to Neurodegeneration

Cited by 99 publications

References 69 publications

Markers of inflammation and microvascular complications in type 1 diabetes

Markers of inflammation and microvascular complications in type 1 diabetes

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

Contact Info

Product

Resources

About