Evidence mapPaperPMID 25720388Full record

Trial reportDiabetes2015

Exenatide Protects Against Glucose- and Lipid-Induced Endothelial Dysfunction: Evidence for Direct Vasodilation Effect of GLP-1 Receptor Agonists in Humans.

Juraj Koska, Michelle Sands, Camelia Burciu, Karen M D'Souza, Kalyani Raravikar, James Liu, Seth Truran, Daniel A Franco, Eric A Schwartz, Dawn C Schwenke and 3 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 7 pooled it
10.3field-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, 7 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Juraj KoskaDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ juraj.koska@va.gov.
Michelle SandsDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Camelia BurciuDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Karen M D'SouzaDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Kalyani RaravikarDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
James LiuDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Seth TruranDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Daniel A FrancoDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Eric A SchwartzDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Dawn C SchwenkeDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
David D'AlessioDivision of Endocrinology, Diabetes and Metabolism, Duke University, Durham, NC.
Raymond Q MigrinoDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Peter D ReavenDepartment of Medicine, Phoenix VA Health Care System, Phoenix, AZ.
Phoenix VA Health Care System · USDuke University · US

Funding

BLRD VA I01 BX001990CSRD VA I01 CX000598NHLBI NIH HHS R21 HL092344NHLBI NIH HHS R21-HL-092344-01NIA NIH HHS R21 AG044723
6 · The paper itself

Abstract

GLP-1 receptor (GLP-1R) agonists may improve endothelial function (EF) via metabolic improvement and direct vascular action. The current study determined the effect of GLP-1R agonist exenatide on postprandial EF in type 2 diabetes and the mechanisms underlying GLP-1R agonist-mediated vasodilation. Two crossover studies were conducted: 36 participants with type 2 diabetes received subcutaneous exenatide or placebo for 11 days and EF, and glucose and lipid responses to breakfast and lunch were determined; and 32 participants with impaired glucose tolerance (IGT) or diet-controlled type 2 diabetes had EF measured before and after intravenous exenatide, with or without the GLP-1R antagonist exendin-9. Mechanisms of GLP-1R agonist action were studied ex vivo on human subcutaneous adipose tissue arterioles and endothelial cells. Subcutaneous exenatide increased postprandial EF independent of reductions in plasma glucose and triglycerides. Intravenous exenatide increased fasting EF, and exendin-9 abolished this effect. Exenatide elicited eNOS activation and NO production in endothelial cells, and induced dose-dependent vasorelaxation and reduced high-glucose or lipid-induced endothelial dysfunction in arterioles ex vivo. These effects were reduced with AMPK inhibition. In conclusion, exenatide augmented postprandial EF in subjects with diabetes and prevented high-glucose and lipid-induced endothelial dysfunction in human arterioles. These effects were largely direct, via GLP-1R and AMPK activation.

Indexed as

AMP-Activated Protein KinasesBlood GlucoseCells, CulturedCross-Over StudiesDiabetes Mellitus, Type 2Double-Blind MethodEndothelial CellsExenatideFemaleGlucagon-Like Peptide-1 ReceptorHumansMalePeptidesReceptors, GlucagonTriglyceridesVasodilationAMP-Activated Protein KinasesBlood GlucoseExenatideGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorPeptidesReceptors, GlucagonTriglyceridesVenoms

Identifiers

PMID25720388
PMCPMC4477348
OpenAlexW2130583827

What Socratic 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 Socratic graph.