Component

Human OCT1-mediated cellular metformin uptake

Human OCT1-mediated cellular metformin uptake. Species, exposure and limitations are retained in each linked claim.

2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. Simultaneous substitution of transmembrane helices TMH2 and TMH3 reversed the affinity for metformin in human-mouse chimeric OCT1.

    The human OCT1 transmembrane helix 2 and 3 pair in the 2020 chimera study → Human OCT1-mediated cellular metformin uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"}
    experimental_model
    Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling
    exposure
    Metformin and thiamine uptake kinetics; transmembrane-helix substitutions
    limitations
    A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human and mouse orthologues side by side
    plain_language
    Two helices carry the species difference in how tightly the drug binds.
    primary_references
    [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170
    tissue_or_cell_type
    Hepatic uptake

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 346–357

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling · source_derived_draft · unverified_draft

    ### metformin-oct1-tmh-determinant Simultaneous substitution of transmembrane helices TMH2 and TMH3 reversed the affinity for metformin in human-mouse chimeric OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Two helices carry the species difference in how tightly the drug binds. organism: Human and mouse orthologues side by side tissue_or_cell_type: Hepatic uptake experimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling limitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement. exposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions evidence_span: {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"} [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170
    Complete structured claim and evidence

  2. Seven non-synonymous OCT1 polymorphisms showed reduced metformin uptake, including OCT1-420del, which has normal activity for model substrates.

    Human OCT1 reduced-function coding variants in the 2007 and 2015 studies → Human OCT1-mediated cellular metformin uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}
    experimental_model
    Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies
    exposure
    Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests
    limitations
    Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Mouse and human, stated per record
    plain_language
    A transporter can look normal on a test substrate and still handle this drug poorly.
    primary_references
    [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    tissue_or_cell_type
    Hepatocytes and whole body
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 125–136

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

    ### metformin-oct1-variants-uptake Seven non-synonymous OCT1 polymorphisms showed reduced metformin uptake, including OCT1-420del, which has normal activity for model substrates. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: A transporter can look normal on a test substrate and still handle this drug poorly. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards