ArticleJournal of cellular and molecular medicine2016
Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Effects of empagliflozin and metformin on biofilm formation and pathogenicity factors of urinary Escherichia coli isolates.Folia microbiologica · 2026Article
- Effects of Elevated Glucose on Bacterial Respiratory Infections in Cystic Fibrosis and Chronic Airway Diseases.International journal of molecular sciences · 2025Review
- Effects of Hypoglycemic Agents on Pulmonary Diseases: A Comprehensive Narrative Review.Journal of inflammation research · 2025Review
- Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.Frontiers in pharmacology · 2025Review
- Obesity Inhibits Alveolar Macrophage Responses to Pseudomonas aeruginosa Pneumonia via Upregulation of Prostaglandin E2 in Male, but Not Female, Mice.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The presence of cystic fibrosis-related diabetes modifies the sputum microbiome in cystic fibrosis disease.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Targeting AMP-activated protein kinase in sepsis.Frontiers in endocrinology · 2024Review
- Clinical impact of metformin exposure during Staphylococcus aureus bacteremia in patients with diabetes mellitus.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Observational
- Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- Airway Epithelial Cell Junctions as Targets for Pathogens and Antimicrobial Therapy.Pharmaceutics · 2022Review
- Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?Medicina (Kaunas, Lithuania) · 2022Review
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Senescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease.Medicina (Kaunas, Lithuania) · 2022Review
- The Role ofToxins · 2021Review
- Synergistic effects of silver ions and metformin against enterococcus faecalis under high-glucose conditions in vitro.BMC microbiology · 2021Article
- A geroscience perspective on immune resilience and infectious diseases: a potential case for metformin.GeroScience · 2021Review
- Cystic fibrosis-related diabetes and lung disease: an update.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.Frontiers in endocrinology · 2021Review
- Influence of Hypoxia on the Epithelial-Pathogen Interactions in the Lung: Implications for Respiratory Disease.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.
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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 OpenQuestion graph.