Trial reportPloS one2012
Pharmacogenetics meets metabolomics: discovery of tryptophan as a new endogenous OCT2 substrate related to metformin disposition.
Trial report in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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.
Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- Organic cation transporter variation and response to smoking cessation therapies.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014Trial
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- Article
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes.International journal of medical sciences · 2023Review
- Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation.Molecules (Basel, Switzerland) · 2021Review
- Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder.Pharmacological research · 2019Review
- Prenatal metformin exposure or organic cation transporter 3 knock-out curbs social interaction preference in male mice.Pharmacological research · 2019Article
- Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy.Clinical and translational science · 2018Review
- Sphingolipid Metabolic Pathway Impacts Thiazide Diuretics Blood Pressure Response: Insights From Genomics, Metabolomics, and Lipidomics.Journal of the American Heart Association · 2017Article
- Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin.The pharmacogenomics journal · 2017Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Article
- Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans.Frontiers in pharmacology · 2016Article
- Article
- Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats.Molecules (Basel, Switzerland) · 2015Article
- Technical and clinical aspects of cortisol as a biochemical marker of chronic stress.BMB reports · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic polymorphisms of the organic cation transporter 2 (OCT2), encoded by SLC22A2, have been investigated in association with metformin disposition. A functional decrease in transport function has been shown to be associated with the OCT2 variants. Using metabolomics, our study aims at a comprehensive monitoring of primary metabolite changes in order to understand biochemical alteration associated with OCT2 polymorphisms and discovery of potential endogenous metabolites related to the genetic variation of OCT2. Using GC-TOF MS based metabolite profiling, clear clustering of samples was observed in Partial Least Square Discriminant Analysis, showing that metabolic profiles were linked to the genetic variants of OCT2. Tryptophan and uridine presented the most significant alteration in SLC22A2-808TT homozygous and the SLC22A2-808G>T heterozygous variants relative to the reference. Particularly tryptophan showed gene-dose effects of transporter activity according to OCT2 genotypes and the greatest linear association with the pharmacokinetic parameters (Cl(renal), Cl(sec), Cl/F/kg, and Vd/F/kg) of metformin. An inhibition assay demonstrated the inhibitory effect of tryptophan on the uptake of 1-methyl-4-phenyl pyrinidium in a concentration dependent manner and subsequent uptake experiment revealed differential tryptophan-uptake rate in the oocytes expressing OCT2 reference and variant (808G>T). Our results collectively indicate tryptophan can serve as one of the endogenous substrate for the OCT2 as well as a biomarker candidate indicating the variability of the transport activity of OCT2.
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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.