{"id":"6a6c6b45-1c2c-52db-a864-eeda0069bbaf","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-oct1-thiamine-substrate","predicate":"transports","statement":"Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"abd213d9-96c0-5fc0-9474-6ee8a7911f47","mechanism_event_label":"The transporter that carries the drug into the liver normally carries vitamin B1.","subject":{"id":"3cced77c-b044-5d97-8c81-4ff9ed3dd169","slug":"slc22a1","display_name":"Human organic cation transporter 1 / OCT1 / SLC22A1","entity_type_key":"protein"},"object":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"abd213d9-96c0-5fc0-9474-6ee8a7911f47","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-oct1-thiamine-substrate-event","event_type":"biochemical_relationship","label":"The transporter that carries the drug into the liver normally carries vitamin B1.","description":"Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f65b84dd-b471-5c59-a229-97770436bb53","slug":"cellular-thiamine-uptake","display_name":"Cellular free-thiamine uptake","entity_type_key":"cellular_process"},"role":"affected_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3cced77c-b044-5d97-8c81-4ff9ed3dd169","slug":"slc22a1","display_name":"Human organic cation transporter 1 / OCT1 / SLC22A1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/24961373.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70\", \"start_char\": 0, \"end_char\": 1270, \"text_sha256\": \"77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Mouse and human transporter","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The transporter that carries the drug into the liver normally carries vitamin B1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver and intestine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"transport_effect","value_text":"raises","comparator":null,"unit":null,"notes":"Identified by isotopic uptake as a principal endogenous substrate.","entity":null},{"dimension":"transport_pool","value_text":"the expressing cell","comparator":null,"unit":null,"notes":"Identified by isotopic uptake as a principal endogenous substrate.","entity":null}],"evidence":[{"id":"4c2e2142-d617-5e4e-b358-635d50aec1f8","evidence_kind":"source_excerpt","locator":"Lines 1230-1241","start_line":1230,"end_line":1241,"excerpt":"### metformin-oct1-thiamine-substrate\nMetabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1.\nCondition category: normal\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: The transporter that carries the drug into the liver normally carries vitamin B1.\norganism: Mouse and human transporter\ntissue_or_cell_type: Liver and intestine\nexperimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake\nlimitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.\nexposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/24961373.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70\", \"start_char\": 0, \"end_char\": 1270, \"text_sha256\": \"77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70\"}\n[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111","model_system":"Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"0b51d0759aeeb88ac5b3a6277245a196b2bb024d7c32ec89379ed428fb06bfb5","revision_id":"0405c75e-f06e-5af7-a642-1777802f6004","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}