Evidence map›Paper›PMID 24162587›Full record

ArticleDiabetologia2014

Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes.

Olaf Brouwers, Petra M G Niessen, Toshio Miyata, Jakob A Østergaard, Allan Flyvbjerg, Carine J Peutz-Kootstra, Jonas Sieber, Peter H Mundel, Michael Brownlee, Ben J A Janssen and 3 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Chinese medical journal · 2018
    Pooled it
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  16. Dicarbonyl Stress in Diabetic Vascular Disease.International journal of molecular sciences · 2022
    Review
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  18. Article
  19. Review
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 4 countries.

Olaf BrouwersLaboratory for Metabolism and Vascular Medicine, Division of General Internal Medicine, Department of Internal Medicine, Maastricht University Medical Center, Universiteitssingel 50, P.O. Box 616 (box 14), 6200 MD, Maastricht, the Netherlands, olaf.brouwers@maastrichtuniversity.nl.
Petra M G Niessen
Toshio Miyata
Jakob A Østergaard
Allan Flyvbjerg
Carine J Peutz-Kootstra
Jonas Sieber
Peter H Mundel
Michael Brownlee
Ben J A Janssen
Jo G R De Mey
Coen D A Stehouwer
Casper G Schalkwijk
Maastricht University · NLUniversity Medical Center · USAarhus University · DKAarhus University Hospital · DKAlbert Einstein College of Medicine · USHarvard University · USMassachusetts General Hospital · USTohoku University · JP

Funding

Role of B7-1 in Podocytes in Pathogenesis of ProteinuriaR01DK062472 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SOBERMAN, ROY · 2004 to 2017
$5.3M
CELL AND MOLECULAR BIOLOGICAL ANALYSIS OF SYNAPTOPODINR01DK057683 · NIDDK · YESHIVA UNIVERSITY · PI SOBERMAN, ROY · 2001 to 2015
$4.8M
NIDDK NIH HHS DK57683NIDDK NIH HHS DK62472
6 · The paper itself

Abstract

aims/hypothesisIn diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes.

methodsWild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection of streptozotocin. Mesenteric arteries were isolated to study ex vivo vascular reactivity with a wire myograph and kidneys were processed for histological examination. Glycation was determined by mass spectrometry and immunohistochemistry. Markers for inflammation, endothelium dysfunction and renal dysfunction were measured with ELISA-based techniques.

resultsDiabetes-induced formation of AGEs in mesenteric arteries and endothelial dysfunction were reduced by Glo1 overexpression. Despite the absence of advanced nephrotic lesions, early markers of renal dysfunction (i.e. increased glomerular volume, decreased podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation and endothelium dysfunction markers. In fully differentiated cultured podocytes incubation with MGO resulted in apoptosis. CONCLUSIONS/

interpretationThis study shows that effective regulation of the GLO-I enzyme is important in the prevention of vascular intracellular glycation, endothelial dysfunction and early renal impairment in experimental diabetes. Modulating the GLO-I pathway therefore may provide a novel approach to prevent vascular complications in diabetes.

Indexed as

AnimalsDiabetes MellitusImmunohistochemistryLactoylglutathione LyaseMalePyruvaldehydeRatsRats, TransgenicLactoylglutathione LyasePyruvaldehyde

Identifiers

PMID24162587
OpenAlexW2025176077

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.