Evidence map›Paper›PMID 29588466›Full record

ArticleScientific reports2018

Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms.

Sarah J Mancini, Daria Boyd, Omar J Katwan, Anastasiya Strembitska, Tarek A Almabrouk, Simon Kennedy, Timothy M Palmer, Ian P Salt

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 2 pooled it
16.8field-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

130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 234 citations in OpenAlex.

  1. Pooled it
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  7. The endothelium response to kidney injury.Nature reviews. Nephrology · 2026
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70 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

8 authors at 4 institutions in 3 countries.

Sarah J ManciniInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Daria BoydInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Omar J KatwanInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Anastasiya StrembitskaInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Tarek A AlmabroukInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Simon KennedyInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.ORCID 0000-0003-0887-5840
Timothy M PalmerSchool of Pharmacy and Medical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
Ian P SaltInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK. Ian.Salt@glasgow.ac.uk.ORCID 0000-0003-0055-3724
University of Glasgow · GBAl Zawiya University · LYUniversity of Bradford · GBUniversity of Diyala · IQ

Funding

British Heart Foundation FS/14/61/31284British Heart Foundation FS/16/55/32731British Heart Foundation PG/12/1/29276British Heart Foundation PG/13/82/30483
6 · The paper itself

Abstract

Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells. Incubation with clinically-relevant concentrations of canagliflozin, but not empagliflozin or dapagliflozin activated AMPK and inhibited IL-1β-stimulated adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated by expression of dominant-negative AMPK and was mimicked by the direct AMPK activator, A769662. Stimulation of cells with either canagliflozin or A769662 had no effect on IL-1β-stimulated cell surface levels of adhesion molecules or nuclear factor-κB signalling. Despite these identical effects of canagliflozin and A769662, IL-1β-stimulated IL-6/MCP-1 mRNA was inhibited by canagliflozin, but not A769662, whereas IL-1β-stimulated c-jun N-terminal kinase phosphorylation was inhibited by A769662, but not canagliflozin. These data indicate that clinically-relevant canagliflozin concentrations directly inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK-dependent and -independent mechanisms without affecting early IL-1β signalling.

Indexed as

AMP-Activated Protein KinasesAnimalsAnti-Inflammatory AgentsCanagliflozinCells, CulturedChemokinesCytokinesEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsInterleukin-1betaMiceSodium-Glucose Transporter 2 InhibitorsAMP-Activated Protein KinasesAnti-Inflammatory AgentsCanagliflozinChemokinesCytokinesInterleukin-1betaSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID29588466
PMCPMC5869674
OpenAlexW2795806738

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.