ArticlePharmacogenetics and genomics2010
Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin.
Article in Pharmacogenetics and genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis.Frontiers in public health · 2023Pooled it
- Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma.Scientific reports · 2019Trial
- Determinants of maternal triglycerides in women with gestational diabetes mellitus in the Metformin in Gestational Diabetes (MiG) study.Diabetes care · 2013Trial
- Gene-Guided Therapy in Type 2 Diabetes Mellitus: An Integrative Review of the Pharmacogenetics of Metformin and Sodium-Glucose Cotransporter-2 Inhibitors.Endocrinology, diabetes & metabolism · 2026Review
- Comprehensive Analysis of Bulk RNA-seq, Machine Learning, Mendelian Randomization, and Single-Cell Sequencing Unravels SLC22A3 as a Solute Carrier Superfamily-Associated Biomarker in Atherosclerosis.Journal of cardiovascular translational research · 2026Article
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- Guilty by association: direct interaction with the tetraspanin CD63 suggests a role for organic cation transporter 3 in histamine release from granulocytes.Journal of biomedical science · 2025Article
- Down-Regulation of HLA-C Expression on Melanocytes May Contribute to the Therapeutic Efficacy of UVB Phototherapy in Psoriasis.International journal of molecular sciences · 2025Article
- The population-specific Thr44Met OCT3 coding variant affects metformin pharmacokinetics with subsequent effects on insulin sensitivity in C57Bl/6J mice.Diabetologia · 2025Article
- Diverse Applications of the Anti-Diabetic Drug Metformin in Treating Human Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus.Acta pharmaceutica Sinica. B · 2024Review
- Advancements in precision medicine: multi-omics approach for tailored metformin treatment in type 2 diabetes.Frontiers in pharmacology · 2024Review
- Genetic preservation of SLC22A3 in the Admixed and Xhosa populations living in the Western Cape.Molecular biology reports · 2023Article
- The Differential Effect of Metformin on Osteocytes, Osteoblasts, and Osteoclasts.Current osteoporosis reports · 2023Review
- Connective tissue mast cells store and release noradrenaline.The journal of physiological sciences : JPS · 2023Article
- Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-naïve type 2 diabetes.Journal of endocrinological investigation · 2023Article
- Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers.Journal of personalized medicine · 2023Article
- The Risk of Age-Related Macular Degeneration Is Reduced in Type 2 Diabetes Patients Who Use Metformin.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesThe goals of this study were to determine the role of organic cation transporter 3 (OCT3) in the pharmacological action of metformin and to identify and functionally characterize genetic variants of OCT3 with respect to the uptake of metformin and monoamines.
methodsFor pharmacological studies, we evaluated metformin-induced activation of AMP-activated protein kinase, a molecular target of metformin. We used quantitative PCR and immunostaining to localize the transporter and isotopic uptake studies in cells transfected with OCT3 and its nonsynonymous genetic variants for functional analyses.
resultsQuantitative PCR and immunostaining showed that OCT3 was expressed high on the plasma membrane of skeletal muscle and liver, target tissues for metformin action. Both the OCT inhibitor, cimetidine, and OCT3-specific short hairpin RNA significantly reduced the activating effect of metformin on AMP-activated protein kinase. To identify genetic variants in OCT3, we used recent data from the 1000 Genomes and the Pharmacogenomics of Membrane Transporters projects. Six novel missense variants were identified. In functional assays, using various monoamines and metformin, three variants, T44M (c.131C>T), T400I (c.1199C>T) and V423F (c.1267G>T) showed altered substrate specificity. Notably, in cells expressing T400I and V423F, the uptakes of metformin and catecholamines were significantly reduced, but the uptakes of metformin, 1-methyl-4-phenylpyridinium and histamine by T44M were significantly increased more than 50%. Structural modeling suggested that these two variants may be located in the pore lining (T400) or proximal (V423) membrane-spanning helixes.
conclusionOur study suggests that OCT3 plays a role in the therapeutic action of metformin and that genetic variants of OCT3 may modulate metformin and catecholamine action.
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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.