Evidence map›Paper›PMID 23984879›Full record

ArticleCardiovascular diabetology2013

Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor.

Yuji Ishibashi, Takanori Matsui, Sayaka Maeda, Yuichiro Higashimoto, Sho-ichi Yamagishi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 1 pooled it
11.5field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.

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  15. Incretin-based therapy: a new horizon in diabetes management.Journal of diabetes and metabolic disorders · 2024
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37 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

5 authors at 2 institutions in 1 country.

Yuji IshibashiDepartment of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. shoichi@med.kurume-u.ac.jp.
Takanori Matsui
Sayaka Maeda
Yuichiro Higashimoto
Sho-ichi Yamagishi
Kurume University · JPKurume University Medical Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdvanced glycation end products (AGEs) and receptor RAGE interaction play a role in diabetic vascular complications. Inhibition of dipeptidyl peptidase-4 (DPP-4) is a potential therapeutic target for type 2 diabetes. However, the role of DPP-4 in AGE-induced endothelial cell (EC) damage remains unclear.

methodsIn this study, we investigated the effects of DPP-4 on reactive oxygen species (ROS) generation and RAGE gene expression in ECs. We further examined whether an inhibitor of DPP-4, linagliptin inhibited AGE-induced soluble DPP-4 production, ROS generation, RAGE, intercellular adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1) gene expression in ECs.

resultsDPP-4 dose-dependently increased ROS generation and RAGE gene expression in ECs, which were prevented by linagliptin. Mannose 6-phosphate (M6P) and antibodies (Ab) raised against M6P/insulin-like growth factor II receptor (M6P/IGF-IIR) completely blocked the ROS generation in DPP-4-exposed ECs, whereas surface plasmon resonance revealed that DPP-4 bound to M6P/IGF-IIR at the dissociation constant of 3.59 x 10⁻⁵ M. AGEs or hydrogen peroxide increased soluble DPP-4 production by ECs, which was prevented by N-acetylcysteine, RAGE-Ab or linagliptin. Linagliptin significantly inhibited the AGE-induced ROS generation, RAGE, ICAM-1 and PAI-1 gene expression in ECs.

conclusionsThe present study suggests that AGE-RAGE-induced ROS generation stimulates the release of DPP-4 from ECs, which could in turn act on ECs directly via the interaction with M6P/IGF-IIR, further potentiating the deleterious effects of AGEs. The blockade by linagliptin of positive feedback loop between AGE-RAGE axis and DPP-4 might be a novel therapeutic target for vascular injury in diabetes.

Indexed as

Cells, CulturedDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDose-Response Relationship, DrugGlycation End Products, AdvancedHumansHuman Umbilical Vein Endothelial CellsIntercellular Adhesion Molecule-1Oxidative StressParacrine CommunicationPlasminogen Activator Inhibitor 1Reactive Oxygen SpeciesReceptor for Advanced Glycation End ProductsReceptor, IGF Type 2Receptors, ImmunologicSignal Transductioncation-dependent mannose-6-phosphate receptorDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDPP4 protein, humanGlycation End Products, AdvancedICAM1 protein, humanIntercellular Adhesion Molecule-1Plasminogen Activator Inhibitor 1Reactive Oxygen SpeciesReceptor for Advanced Glycation End ProductsReceptor, IGF Type 2Receptors, ImmunologicSERPINE1 protein, human

Identifiers

PMID23984879
PMCPMC3765742
OpenAlexW2119198856

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Registered trials

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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.