ArticleThe Journal of biological chemistry2014
Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04448821 (A Clinical Trial to Evaluate the Effect of Nilotinib on the Pharmacokinetics and Pharmacodynamics of Metformin in Healthy Male Adults), which is not on this map. Cited by 51 papers.
What it found
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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.
A Clinical Trial to Evaluate the Effect of Nilotinib on the Pharmacokinetics and Pharmacodynamics of Metformin in Healthy Male Adults
Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers.European journal of drug metabolism and pharmacokinetics · 2025Trial
- Improved glycemic control with minimal systemic metformin exposure: Effects of Metformin Delayed-Release (Metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes.PloS one · 2018 · on this mapTrial
- Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials.Diabetologia · 2016 · on this mapTrial
- Interindividual variability in metformin pharmacokinetics in pediatric patients.Pediatric research · 2026Article
- Effects of anti-diabetic medications on the teeth, oral soft and hard tissues, saliva, and implants: a scoping review.BDJ open · 2026Review
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Effect of Metformin on Meibomian Gland Epithelial Cells: Implications in Aging and Diabetic Dry Eye Disease.Life (Basel, Switzerland) · 2024Article
- Cardiac Uptake of the Adrenergic Imaging AgentDrug metabolism and disposition: the biological fate of chemicals · 2024Article
- Human ABC and SLC Transporters: The Culprit Responsible for Unspecific PSMA-617 Uptake?Pharmaceuticals (Basel, Switzerland) · 2024Article
- Metformin and the Liver: Unlocking the Full Therapeutic Potential.Metabolites · 2024Review
- Article
- Summarizing studies using constitutive genetic deficiency to investigate behavioural influences of uptake 2 monoamine transporters.Basic & clinical pharmacology & toxicology · 2023Review
- Interaction of ALK Inhibitors with Polyspecific Organic Cation Transporters and the Impact of Substrate-Dependent Inhibition on the Prediction of Drug-Drug Interactions.Pharmaceutics · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Determination and disposition of meta-iodobenzylguanidine in plasma and heart of transporter-deficient mice by UPLC-MS/MS.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Article
- MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Drug-induced taste disturbance is a common adverse drug reaction often triggered by drug secretion into saliva. Very little is known regarding the molecular mechanisms underlying salivary gland transport of xenobiotics, and most drugs are assumed to enter saliva by passive diffusion. In this study, we demonstrate that salivary glands selectively and highly express OCT3 (organic cation transporter-3), a polyspecific drug transporter in the solute carrier 22 family. OCT3 protein is localized at both basolateral (blood-facing) and apical (saliva-facing) membranes of salivary gland acinar cells, suggesting a dual role of this transporter in mediating both epithelial uptake and efflux of organic cations in the secretory cells of salivary glands. Metformin, a widely used anti-diabetic drug known to induce taste disturbance, is transported by OCT3/Oct3 in vitro. In vivo, metformin was actively transported with a high level of accumulation in the salivary glands of wild-type mice. In contrast, active uptake and accumulation of metformin in salivary glands were abolished in Oct3(-/-) mice. Oct3(-/-) mice also showed altered metformin pharmacokinetics and reduced drug exposure in the heart. These results demonstrate that OCT3 is responsible for metformin accumulation and secretion in salivary glands. Our study uncovered a novel carrier-mediated pathway for drug entry into saliva and sheds new light on the molecular mechanisms underlying drug-induced taste disorders.
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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.