ArticlePLoS biology2018
Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans.International journal of molecular sciences · 2026Article
- Transporters in vitamin uptake and cellular metabolism: impacts on health and disease.Life metabolism · 2025Review
- Clozapine impaired glucose-stimulated insulin secretion partly by increasing plasma 5-HT levels due to the inhibition of OCT1-mediated hepatic 5-HT uptake in mice.Acta pharmacologica Sinica · 2025Article
- Article
- OCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids.Scientific reports · 2024Article
- The full spectrum of SLC22 OCT1 mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics.Molecular cell · 2024Article
- Thiamine deficiency in diabetes, obesity and bariatric surgery: Recipes for diabetic ketoacidosis.Journal of family medicine and primary care · 2024Review
- In Vitro and In Silico Studies on Cytotoxic Properties of Oxythiamine and 2'-Methylthiamine.International journal of molecular sciences · 2024Article
- Effects of Cinnamon Powder on Glucose Metabolism in Diabetic Mice and the Molecular Mechanisms.Foods (Basel, Switzerland) · 2023Article
- The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.Metabolites · 2023Article
- The full spectrum of OCT1 (SLC22A1) mutations bridges transporter biophysics to drug pharmacogenomics.bioRxiv : the preprint server for biology · 2023Article
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- In Vitro Characterization of Renal Drug Transporter Activity in Kidney Cancer.International journal of molecular sciences · 2022Article
- New and Emerging Research on Solute Carrier and ATP Binding Cassette Transporters in Drug Discovery and Development: Outlook From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Relationships between Inhibition, Transport and Enhanced Transport via the Organic Cation Transporter 1.International journal of molecular sciences · 2022Article
- Article
- SLC22 Transporters in the Fly Renal System Regulate Response to Oxidative Stress In Vivo.International journal of molecular sciences · 2021Article
- Review
- Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation.Molecules (Basel, Switzerland) · 2021Review
- Drugs in COVID-19 Clinical Trials: Predicting Transporter-Mediated Drug-Drug Interactions Using In Vitro Assays and Real-World Data.Clinical pharmacology and therapeutics · 2021Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
A constellation of metabolic disorders, including obesity, dysregulated lipids, and elevations in blood glucose levels, has been associated with cardiovascular disease and diabetes. Analysis of data from recently published genome-wide association studies (GWAS) demonstrated that reduced-function polymorphisms in the organic cation transporter, OCT1 (SLC22A1), are significantly associated with higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels and an increased risk for type 2 diabetes mellitus, yet the mechanism linking OCT1 to these metabolic traits remains puzzling. Here, we show that OCT1, widely characterized as a drug transporter, plays a key role in modulating hepatic glucose and lipid metabolism, potentially by mediating thiamine (vitamin B1) uptake and hence its levels in the liver. Deletion of Oct1 in mice resulted in reduced activity of thiamine-dependent enzymes, including pyruvate dehydrogenase (PDH), which disrupted the hepatic glucose-fatty acid cycle and shifted the source of energy production from glucose to fatty acids, leading to a reduction in glucose utilization, increased gluconeogenesis, and altered lipid metabolism. In turn, these effects resulted in increased total body adiposity and systemic levels of glucose and lipids. Importantly, wild-type mice on thiamine deficient diets (TDs) exhibited impaired glucose metabolism that phenocopied Oct1 deficient mice. Collectively, our study reveals a critical role of hepatic thiamine deficiency through OCT1 deficiency in promoting the metabolic inflexibility that leads to the pathogenesis of cardiometabolic disease.
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