Evidence map›Paper›PMID 23390498›Full record

ArticlePloS one2013

Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?

Usha Panchapakesan, Kate Pegg, Simon Gross, Muralikrishna Gangadharan Komala, Harshini Mudaliar, Josephine Forbes, Carol Pollock, Amanda Mather

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

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 7 pooled it
11.9field-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

145 citing papers in PubMed, 7 syntheses or guidelines pooled it, 273 citations in OpenAlex.

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85 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 3 institutions in 1 country.

Usha PanchapakesanDepartment of Medicine, The University of Sydney, Renal Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales, Australia. usha.panchapakesan@sydney.edu.au
Kate Pegg
Simon Gross
Muralikrishna Gangadharan Komala
Harshini Mudaliar
Josephine Forbes
Carol Pollock
Amanda Mather
Royal North Shore Hospital · AUUniversity of Sydney · AUMater Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sodium/glucose cotransporter 2 (SGLT2) inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2, the primary glucose transporter in the proximal tubular cell (PTC), leading to glycosuria and lowering of serum glucose. We examined the renoprotective effects of the SGLT2 inhibitor empagliflozin to determine whether blocking glucose entry into the kidney PTCs reduced the inflammatory and fibrotic responses of the cell to high glucose. We used an in vitro model of human PTCs. HK2 cells (human kidney PTC line) were exposed to control 5 mM, high glucose (HG) 30 mM or the profibrotic cytokine transforming growth factor beta (TGFβ1; 0.5 ng/ml) in the presence and absence of empagliflozin for up to 72 h. SGLT1 and 2 expression and various inflammatory/fibrotic markers were assessed. A chromatin immunoprecipitation assay was used to determine the binding of phosphorylated smad3 to the promoter region of the SGLT2 gene. Our data showed that TGFβ1 but not HG increased SGLT2 expression and this occurred via phosphorylated smad3. HG induced expression of Toll-like receptor-4, increased nuclear deoxyribonucleic acid binding for nuclear factor kappa B (NF-κB) and activator protein 1, induced collagen IV expression as well as interleukin-6 secretion all of which were attenuated with empagliflozin. Empagliflozin did not reduce high mobility group box protein 1 induced NF-κB suggesting that its effect is specifically related to a reduction in glycotoxicity. SGLT1 and GLUT2 expression was not significantly altered with HG or empagliflozin. In conclusion, empagliflozin reduces HG induced inflammatory and fibrotic markers by blocking glucose transport and did not induce a compensatory increase in SGLT1/GLUT2 expression. Although HG itself does not regulate SGLT2 expression in our model, TGFβ increases SGLT2 expression through phosphorylated smad3.

Indexed as

Benzhydryl CompoundsCollagen Type IVDiabetes MellitusDiabetic NephropathiesEpithelial CellsGene ExpressionGlucoseGlucosidesHumansHypoglycemic AgentsInterleukin-6Kidney Tubules, ProximalNF-kappa BPhosphorylationPromoter Regions, GeneticProtein BindingBenzhydryl CompoundsCollagen Type IVempagliflozinGlucoseGlucosidesHypoglycemic AgentsIL6 protein, humanInterleukin-6NF-kappa BSLC5A1 protein, humanSLC5A2 protein, humanSmad3 ProteinSMAD3 protein, humanSodium-Glucose Transporter 1Sodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsTLR4 protein, humanToll-Like Receptor 4Transcription Factor AP-1Transforming Growth Factor beta1

Identifiers

PMID23390498
PMCPMC3563635
OpenAlexW2085015828

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.