Association of reduced glyoxalase 1 activity and painful peripheral diabetic neuropathy in type 1 and 2 diabetes mellitus patients

Skapare, Elina; Konrāde, Ilze; Liepinsh, Edgars; Strēle, Ieva; Makrecka, Marina; Bierhaus, Angelika; Lejnieks, Aivars; Pīrāgs, Valdis; Dambrova, Maija

doi:10.1016/j.jdiacomp.2012.12.002

Cited by 45 publications

(36 citation statements)

References 36 publications

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“…AGEs increase both oxidative stress and inflammation and participate in the pathogenesis of diabetic microvascular complications and especially DN . Skapare E et al demonstrated lower activity of the gene in T1D and T2D patients with painful DN. This supports the hypothesis that GLO1 activity prevents the appearance of painful DN.…”

Section: Genetic Markers Of Diabetic Neuropathy Developmentmentioning

confidence: 99%

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Kallinikou

Soldatou

Tsentidis

et al. 2019

Diabetes Metabolism Res

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Summary Diabetic neuropathy (DN) is a common long‐term complication of type 1 (T1D) and type 2 (T2D) diabetes mellitus, with significant morbidity and mortality. DN is defined as impaired function of the autonomic and/or peripheral nervous system, often subclinical, particularly in children and adolescents with T1D. Nerve conduction studies (NCS) and skin biopsies are considered gold‐standard methods in the assessment of DN. Multiple environmental and genetic factors are involved in the pathogenesis of DN. Specifically, the role of metabolic control and glycemic variability is of paramount importance. A number of recently identified genes, including the AKR1B1, VEGF, MTHFR, APOE, and ACE genes, contribute significantly in the pathogenesis of DN. These genes may serve as biomarkers to predict future DN development or treatment response. In addition, they may serve as the basis for the development of new medications or gene therapy. In this review, the diagnostic evaluation, pathogenesis, and associated genetic markers of DN in children and adolescents with T1D are presented and discussed.

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Section: Genetic Markers Of Diabetic Neuropathy Developmentmentioning

confidence: 99%

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Kallinikou

Soldatou

Tsentidis

et al. 2019

Diabetes Metabolism Res

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“…In the literature on painful diabetic neuropathy, lower glyoxalase activity is observed in disease subjects and leads to heavier carbonyl stress [65,66]. Whether it is up-regulated or down-regulated, the glyoxalase system is overwhelmed by hyperglycemia-induced MGO overproduction.…”

Section: Resultsmentioning

confidence: 99%

Evolving Evidence of Methylglyoxal and Dicarbonyl Stress Related Diseases from Diabetic to Non-Diabetic Models

Wang¹,

Lee²,

Chou³

2015

Pharm Anal Acta

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Methylglyoxal (MGO), a byproduct of sugar and lipid metabolic processes, is a major glycating agent. This metabolite reacts with basic residues of proteins and promotes the formation of advanced glycation end products (AGEs). Although MGO and AGEs are widely discussed in the context of diabetes, until recently, MGO was thought to result from insufficient blood sugar control. A new report reveals that plasma MGO, and not blood sugar, distinguishes diabetic patients with no pain from those with pain. This ability brings to MGO a new applicability to disease diagnosis.Diseases with normal sugar conditions, such as hypertension, sepsis, and renal disease, are increasingly recognized as MGO-related. We review the role of MGO in drug-induced nephropathy, induction of hypertension by oral administration, and as a biomarker of sepsis. We also discuss the measurement of MGO and its stable metabolite d-lactate.The metabolism and pathogenic mechanisms of MGO need investigation in diverse disease models. Whether MGO can be considered as an individual pathological factor will be an interesting topic.

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“…Although a correlation between a SNP in Glo1 and diabetic neuropathy among type 2 diabetics has been reported in humans, the effect was not statistically significant when corrected for multiple comparisons [34]. Recent work has demonstrated decreased GLO1 activity in patients with painful diabetic neuropathy as compared to those with painless diabetic neuropathy, suggesting a role for GLO1 in pain [33]. The mechanism of MG-induced hyperalgesia has been attributed to protein modification and activation of TRPA1 receptors [21,66].…”

Section: Therapeutic Potential Of Glo1 Inhibitorsmentioning

confidence: 99%

Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development

McMurray

Distler

Sidhu

et al. 2014

Biochemical Society Transactions

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Many current pharmacological treatments for neuropsychiatric disorders, such as anxiety and depression, are limited by a delayed onset of therapeutic effect, adverse side effects, abuse potential or lack of effect in many patients. These off-target effects highlight the need to identify novel mechanisms and targets for treatment. Recently, modulation of glyoxalase 1 (GLO1) activity was shown to regulate anxiety-like behavior and seizure susceptibility in mice. These effects are likely mediated through the regulation of methylglyoxal (MG) by GLO1, as MG acts as a competitive partial agonist at GABAA receptors (GABAARs). Thus, modulation of MG by GLO1 represents a novel target for treatment. Here, we evaluate the therapeutic potential of indirectly modulating MG concentrations through GLO1 inhibitors for the treatment of neuropsychiatric disorders.

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Association of reduced glyoxalase 1 activity and painful peripheral diabetic neuropathy in type 1 and 2 diabetes mellitus patients

Cited by 45 publications

References 36 publications

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Evolving Evidence of Methylglyoxal and Dicarbonyl Stress Related Diseases from Diabetic to Non-Diabetic Models

Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development

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