Cited by 313Aldose Reductase and TaurinePain Mechanisms and TreatmentsPeripheral Neuropathies and Disorders

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Metabolic and Vascular Factors in the Pathogenesis of Diabetic Neuropathy

Cameron, Norman E, Cotter, Mary A·1997·Diabetes

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Abstract

Reduced nerve perfusion is an important factor in the etiology of diabetic neuropathy. Studies in streptozotocin-induced diabetic rats show that nerve conduction velocity (NCV) and blood flow deficits are corrected by treatment with vasodilator drugs, with angiotensin II and endothelin-1 antagonists being particularly important. The AT1 antagonist ZD7155 also prevents diabetic deficits in regeneration following nerve damage, indicating that hypoperfusion is an important limitation for nerve repair. Metabolic changes include high polyol pathway flux, increased advanced glycosylation, elevated oxidative stress, and impaired ω-6 essential fatty acid metabolism. Aldose reductase inhibitors (ARIs) restore NCV via their effects on perfusion. ARI action probably depends on blocking the conversion of glucose to sorbitol, thus preventing depletion of vasa nervorum glutathione, an important endogenous free radical scavenger. Free radicals cause vascular endothelium damage and reduced nitric oxide vasodilation. Inhibition of advanced glycosylation and autoxidation (autoxidative glycosylation), major sources of free radicals, by aminoguanidine or transition metal chelators, corrects neurovascular dysfunction. Evening primrose oil supplies γ-linolenic acid (GLA) to improve vasodilator eicosanoid synthesis in diabetes, correcting nerve blood flow and NCV deficits. Interactions between some of these mechanisms have therapeutic implications. Thus, combined ARI and evening primrose oil treatment produced a 10-fold amplification of NCV and blood flow responses. Similarly, GLA effects are markedly enhanced when given in combination with ascorbate as ascorbyl-GLA. Thus, metabolic abnormalities combine to produce deleterious changes in nerve perfusion that make a major contribution to the etiology of diabetic neuropathy. The potential importance of multi-action therapy is stressed.

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elsalam, S. A., Ragab, M., Kandeil, M. A., et al. (2007) · Journal of Veterinary Medical Research · doi:10.21608/jvmr.2007.77895
“Furthermore, Schroeder et al., (2005) attributed the mechanism of action of LA to its blocking effect on interleukin- 1beta that is secreted by activated macrophages in response to immune- mediated process causing islet cell death in IDDM.”
Background
Sural Nerve Perfusion in Mice
Dudele, A., Rasmussen, P. M., & Østergaard, L. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.579373
“, diabetic peripheral neuropathy (DPN) and neuropathic pain conditions (Cameron and Cotter, 1997; Lim et al., 2015).”
Background

Authors: Cameron, N. E., & Cotter, M. A.
Affiliations: University of Aberdeen (GB)
ORCID: Cameron, Norman E
Cotter, Mary A
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1997-09-01
Volume: 46
Issue: Supplement_2
Pages: S31-S37
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.46.2.s31
OpenAlex: W2151689386
Cited by: 312
References: 0
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 8
FWCI: 4.82
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
Keywords: diabetic neuropathy, nerve blood flow, nerve conduction velocity, polyol pathway, advanced glycation end products, oxidative stress, aldose reductase inhibitors, sorbitol, glutathione, vasa nervorum, angiotensin receptor blockers, nerve regeneration, aminoguanidine, evening primrose oil, gamma-linolenic acid, nitric oxide, vasodilation, free radicals, endothelial injury
MeSH terms: Animals, Carnitine, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Endothelium, Vascular, Fatty Acids, Essential, Glycosylation, Humans, Nerve Tissue, Oxidation-Reduction, Regional Blood Flow, Sugar Alcohols, Vasodilator Agents, Reactive Oxygen Species, Rats

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Metabolic and Vascular Factors in the Pathogenesis of Diabetic Neuropathy

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