Evidence map›Paper›PMID 35887308›Full record

ArticleInternational journal of molecular sciences2022

Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation, Glucose Uptake and Cell Metabolism.

Elmar Zügner, Hsiu-Chiung Yang, Petra Kotzbeck, Beate Boulgaropoulos, Harald Sourij, Sepideh Hagvall, Charles S Elmore, Russell Esterline, Sven Moosmang, Jan Oscarsson and 3 more

Open access · goldFull text read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

18 citing papers in PubMed, 26 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

13 authors at 4 institutions in 3 countries.

Elmar ZügnerInstitute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010 Graz, Austria.ORCID 0000-0001-7124-2793
Hsiu-Chiung YangResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
Petra KotzbeckDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Beate BoulgaropoulosInstitute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010 Graz, Austria.
Harald SourijDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.ORCID 0000-0003-3510-9594
Sepideh HagvallResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
Charles S ElmorePharmaceutical Sciences, R&D, AstraZeneca, 415 25 Göteborg, Sweden.ORCID 0000-0001-7434-8307
Russell EsterlineLate-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Sven MoosmangResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.
Jan OscarssonLate-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Thomas R PieberInstitute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010 Graz, Austria.
Xiao-Rong PengResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 431 83 Gothenburg, Sweden.ORCID 0000-0002-8914-0194
Christoph MagnesInstitute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Neue Stiftingtalstrasse 2, 8010 Graz, Austria.
AstraZeneca (Sweden) · SEJoanneum Research · ATAstraZeneca (United States) · USMedical University of Graz · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

(1) The cardio-reno-metabolic benefits of the SGLT2 inhibitors canagliflozin (cana), dapagliflozin (dapa), ertugliflozin (ertu), and empagliflozin (empa) have been demonstrated, but it remains unclear whether they exert different off-target effects influencing clinical profiles. (2) We aimed to investigate the effects of SGLT2 inhibitors on mitochondrial function, cellular glucose-uptake (GU), and metabolic pathways in human-umbilical-vein endothelial cells (HUVECs). (3) At 100 µM (supra-pharmacological concentration), cana decreased ECAR by 45% and inhibited GU (IC5o: 14 µM). At 100 µM and 10 µM (pharmacological concentration), cana increased the ADP/ATP ratio, whereas dapa and ertu (3, 10 µM, about 10× the pharmacological concentration) showed no effect. Cana (100 µM) decreased the oxygen consumption rate (OCR) by 60%, while dapa decreased it by 7%, and ertu and empa (all 100 µM) had no significant effect. Cana (100 µM) inhibited GLUT1, but did not significantly affect GLUTs' expression levels. Cana (100 µM) treatment reduced glycolysis, elevated the amino acids supplying the tricarboxylic-acid cycle, and significantly increased purine/pyrimidine-pathway metabolites, in contrast to dapa (3 µM) and ertu (10 µM). (4) The results confirmed cana´s inhibition of mitochondrial activity and GU at supra-pharmacological and pharmacological concentrations, whereas the dapa, ertu, and empa did not show effects even at supra-pharmacological concentrations. At supra-pharmacological concentrations, cana (but not dapa or ertu) affected multiple cellular pathways and inhibited GLUT1.

Indexed as

Diabetes Mellitus, Type 2Sodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsCanagliflozinEndothelial CellsGlucoseGlucose Transporter Type 1HumansMitochondriaOxidative PhosphorylationBenzhydryl CompoundsCanagliflozinGlucoseGlucose Transporter Type 1Sodium-Glucose Transporter 2 Inhibitorscanagliflozincell metabolismcellular energy leveldapagliflozinempagliflozinertugliflozinglucose uptakemetabolomicsmitochondrial oxidative phosphorylationSGLT2 inhibitor

Identifiers

PMID35887308
PMCPMC9319636
OpenAlexW4286217235

What Socratic holds

Textfull text, public
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 Socratic graph.