ArticleProceedings of the National Academy of Sciences of the United States of America2014
OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 235 citations in OpenAlex.
- Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.Clinical pharmacology and therapeutics · 2025Trial
- Hepatic exposure of metformin in patients with non-alcoholic fatty liver disease.British journal of clinical pharmacology · 2019Trial
- Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.Clinical pharmacology and therapeutics · 2016Trial
- Advancing Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.Clinical pharmacology and therapeutics · 2026Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- 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
- Context-Dependent Modulation of Ferroptosis by Metformin: Mechanisms, Therapeutic Implications and Open Questions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Adverse events associated with drug-related thiamine deficiency: A pharmacovigilance study.JPEN. Journal of parenteral and enteral nutrition · 2026Article
- Deorphanisation and functional characterisation of OATP5A1 as transport protein for amino acids and vitamins.Cellular & molecular biology letters · 2026Article
- Feed-Forward Deep Neural Networks Predict Substrate-Specific Effects of Transporter Variants to Explain Drug Response Variability.Clinical and translational science · 2026Article
- Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015-2025).Diseases (Basel, Switzerland) · 2026Review
- Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions.Journal of pharmaceutical analysis · 2025Review
- Metformin and Adipose Tissue: A Multifaceted Regulator in Metabolism, Inflammation, and Regeneration.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Thiamine, gastrointestinal beriberi and acetylcholine signaling.Frontiers in nutrition · 2025Review
- Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.Nature communications · 2024Article
- The anticancer effect of metformin targets VDAC1 via ER-mitochondria interactions-mediated autophagy in HCC.Experimental & molecular medicine · 2024Article
- Structural basis of thiamine transport and drug recognition by SLC19A3.Nature communications · 2024Article
- SLC13A3 is a major effector downstream of activated β-catenin in liver cancer pathogenesis.Nature communications · 2024Article
- Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 1 institution in 2 countries.
Funding
Abstract
Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug. However, its endogenous role is poorly understood. Here we show that similar to metformin treatment, loss of Oct1 caused an increase in the ratio of AMP to ATP, activated the energy sensor AMP-activated kinase (AMPK), and substantially reduced triglyceride (TG) levels in livers from healthy and leptin-deficient mice. Conversely, livers of human OCT1 transgenic mice fed high-fat diets were enlarged with high TG levels. Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1. Thiamine deficiency enhanced the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Metformin and the biguanide analog, phenformin, competitively inhibited OCT1-mediated thiamine uptake. Acute administration of metformin to wild-type mice reduced intestinal accumulation of thiamine. These findings suggest that OCT1 plays a role in hepatic steatosis through modulation of energy status. The studies implicate OCT1 as well as metformin in thiamine disposition, suggesting an intriguing and parallel mechanism for metformin and its major hepatic transporter in metabolic function.
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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.