ArticleInternational journal of molecular sciences2022
Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation, Glucose Uptake and Cell Metabolism.
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.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- A putative SGLT-relevant mechanistic perspective on quercetin-3-O-glucoside and rutin in diabetic kidney disease.Diabetology & metabolic syndrome · 2026Review
- Vasculoprotective Effects of Sodium-Glucose Co-Transporter Inhibitors in Non-Diabetic Experimental Settings: A Narrative Review.International journal of molecular sciences · 2026Review
- The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents.Diabetes & metabolism journal · 2026Review
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Effect of empagliflozin on human primary cardiomyocytes in a chemically induced hypoxia by CoClPhysiological reports · 2025Article
- Comparison of the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiac Fibroblast Properties.International journal of molecular sciences · 2025Article
- Canagliflozin Inhibits Electrogenic Na+ Transport in Mouse Cortical Collecting Duct Cells.Function (Oxford, England) · 2025Article
- Mitochondrial Changes Induced by SGLT2i in Lymphocytes from Diabetic Kidney Transplant Recipients: A Pilot Study.International journal of molecular sciences · 2025Article
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
- Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside.Journal of clinical medicine · 2024Review
- Recent advances in understanding the mechanisms in skeletal muscle of interaction between exercise and frontline antihyperglycemic drugs.Physiological reports · 2024Review
- Dapagliflozin promotes browning of white adipose tissue through the FGFR1-LKB1-AMPK signaling pathway.Molecular biology reports · 2024Article
- Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: a drug-target Mendelian randomization study.Frontiers in pharmacology · 2024Article
- Multi-omics analysis reveals attenuation of cellular stress by empagliflozin in high glucose-treated human cardiomyocytes.Journal of translational medicine · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Gliflozins Have an Anti-Inflammatory Effect on Renal Proximal Tubular Epithelial Cells in a Diabetic and Inflammatory Microenvironment In Vitro.International journal of molecular sciences · 2023Article
- Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosisFrontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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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 Socratic graph.