Cited by 488Pain Mechanisms and TreatmentsAldose Reductase and TaurinePeripheral Neuropathies and Disorders

Mechanism of diabetic neuropathy: Where are we now and where to go?

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Yagihashi, Soroku, Mizukami, Hiroki, Sugimoto, Kazuhiro·2011·Journal of Diabetes Investigation

Abstract

Neuropathy is the most common complication of diabetes. As a consequence of longstanding hyperglycemia, a downstream metabolic cascade leads to peripheral nerve injury through an increased flux of the polyol pathway, enhanced advanced glycation end‐products formation, excessive release of cytokines, activation of protein kinase C and exaggerated oxidative stress, as well as other confounding factors. Although these metabolic aberrations are deemed as the main stream for the pathogenesis of diabetic microvascular complications, organ‐specific histological and biochemical characteristics constitute distinct mechanistic processes of neuropathy different from retinopathy or nephropathy. Extremely long axons originating in the small neuronal body are vulnerable on the most distal side as a result of malnutritional axonal support or environmental insults. Sparse vascular supply with impaired autoregulation is likely to cause hypoxic damage in the nerve. Such dual influences exerted by long‐term hyperglycemia are critical for peripheral nerve damage, resulting in distal‐predominant nerve fiber degeneration. More recently, cellular factors derived from the bone marrow also appear to have a strong impact on the development of peripheral nerve pathology. As evident from such complicated processes, inhibition of single metabolic factors might not be sufficient for the treatment of neuropathy, but a combination of several inhibitors might be a promising approach to overcome this serious disorder. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00070.x, 2010)

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  1. [3]Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4400 patients observed. Diabetes Care 1978; 1: 168– 188

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Authors
Yagihashi, S., Mizukami, H., & Sugimoto, K.
Affiliations
Hirosaki University (JP)
Corresponding author
Yagihashi, Soroku
Venue
Journal of Diabetes Investigation
Publisher
Wiley
Published
2010-10-06
Volume
2
Issue
1
Pages
18-32
ISSN
  • 2040-1116 (ISSN-L)
  • 2040-1124
OpenAlex
W1600715668
Cited by
488
References
169
Citations by year
2026: 26 · 2025: 48 · 2024: 38 · 2023: 62 · 2022: 53 · 2021: 56 · 2020: 47 · 2019: 31 · 2018: 37 · 2017: 24 · 2016: 26 · 2015: 18 · 2014: 8 · 2013: 6 · 2012: 6
FWCI
0.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Diabetes Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
diabetic neuropathy, pathogenesis, hyperglycemia, polyol pathway, advanced glycation end products, cytokines, protein kinase C, oxidative stress, peripheral nerve injury, bone marrow-derived cells, combination therapy

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