Evidence map›Paper›PMID 23343509›Full record

ArticleJournal of molecular endocrinology2013

Exendin-4 protects endothelial cells from lipoapoptosis by PKA, PI3K, eNOS, p38 MAPK, and JNK pathways.

Ozlem Erdogdu, Linnéa Eriksson, Hua Xu, Ake Sjöholm, Qimin Zhang, Thomas Nyström

Registry-linked trialOpen access · hybridAbstract read
PubMed Publisher
In one paragraph

Article in Journal of molecular endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02621489 (Effects on Re-endothelialisation With Bydureon Treatment Add on to Insulin Versus Insulin Alone, Both in Combination With Metformin in Type 2 Diabetic Subjects), which is not on this map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.5field-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.

NCT02621489 phase4completedstarted 2015, after this paper: background citation

Effects on Re-endothelialisation With Bydureon Treatment Add on to Insulin Versus Insulin Alone, Both in Combination With Metformin in Type 2 Diabetic Subjects

Ran2015Enrolled38Registered outcomes16Posted comparisons0ConditionsAtherosclerosis, Diabetes, RestenosisArmsBydureon, Humulin kwickpen, Metformin
Open the trial in the graph
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 70 citations in OpenAlex.

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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

6 authors at 2 institutions in 2 countries.

Ozlem ErdogduDepartment of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
Linnéa Eriksson
Hua Xu
Ake Sjöholm
Qimin Zhang
Thomas Nyström
Ningxia Medical University · CNKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Experimental studies have indicated that endothelial cells play an important role in maintaining vascular homeostasis. We previously reported that human coronary artery endothelial cells (HCAECs) express the glucagon-like peptide 1 (GLP1) receptor and that the stable GLP1 mimetic exendin-4 is able to activate the receptor, leading to increased cell proliferation. Here, we have studied the effect of exendin-4 and native GLP1 (7-36) on lipoapoptosis and its underlying mechanisms in HCAECs. Apoptosis was assessed by DNA fragmentation and caspase-3 activation, after incubating cells with palmitate. Nitric oxide (NO) and reactive oxidative species (ROS) were analyzed. GLP1 receptor activation, PKA-, PI3K/Akt-, eNOS-, p38 MAPK-, and JNK-dependent pathways, and genetic silencing of transfection of eNOS were also studied. Palmitate-induced apoptosis stimulated cells to release NO and ROS, concomitant with upregulation of eNOS, which required activation of p38 MAPK and JNK. Exendin-4 restored the imbalance between NO and ROS production in which ROS production decreased and NO production was further augmented. Incubation with exendin-4 and GLP1 (7-36) protected HCAECs against lipoapoptosis, an effect that was blocked by PKA, PI3K/Akt, eNOS, p38 MAPK, and JNK inhibitors. Genetic silencing of eNOS also abolished the anti-apoptotic effect afforded by exendin-4. Our results support the notion that GLP1 receptor agonists restore eNOS-induced ROS production due to lipotoxicity and that such agonists protect against lipoapoptosis through PKA-PI3K/Akt-eNOS-p38 MAPK-JNK-dependent pathways via a GLP1 receptor-dependent mechanism.

Indexed as

ApoptosisCaspase 3Cyclic AMP-Dependent Protein KinasesDNA FragmentationEndothelial CellsEnzyme ActivationExenatideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHumansJNK Mitogen-Activated Protein KinasesNitric Oxide Synthase Type IIIp38 Mitogen-Activated Protein KinasesPalmitatesPeptidesPhosphatidylinositol 3-KinasesCaspase 3Cyclic AMP-Dependent Protein KinasesExenatideGLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorJNK Mitogen-Activated Protein KinasesNitric Oxide Synthase Type IIIp38 Mitogen-Activated Protein KinasesPalmitatesPeptidesPhosphatidylinositol 3-KinasesReactive Oxygen SpeciesReceptors, GlucagonVenoms

Identifiers

PMID23343509
OpenAlexW2096516115

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.