{"id":"fd5d5ec0-fddb-5a81-8170-c548ca677a6a","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-thtr2-species-difference","predicate":"differs_in_affinity_from","statement":"Species differences in the substrate specificity of THTR-2 between the human and mouse orthologues were observed.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"566d2cf5-056c-5726-977f-a50bc3a66f20","mechanism_event_label":"The mouse version of this carrier does not behave like the human one.","subject":{"id":"4eba176e-17c8-5515-920a-df5d48a40486","slug":"slc19a3","display_name":"Human thiamine transporter 2 / SLC19A3","entity_type_key":"protein"},"object":{"id":"d4c2b412-1eca-52bf-9334-6c855497abef","slug":"mouse-slc19a3","display_name":"Mouse thiamine transporter 2 / Slc19a3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"566d2cf5-056c-5726-977f-a50bc3a66f20","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-thtr2-species-difference-event","event_type":"observed_intervention","label":"The mouse version of this carrier does not behave like the human one.","description":"Species differences in the substrate specificity of THTR-2 between the human and mouse orthologues were observed.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4eba176e-17c8-5515-920a-df5d48a40486","slug":"slc19a3","display_name":"Human thiamine transporter 2 / SLC19A3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d4c2b412-1eca-52bf-9334-6c855497abef","slug":"mouse-slc19a3","display_name":"Mouse thiamine transporter 2 / Slc19a3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/26528626.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\", \"start_char\": 0, \"end_char\": 1436, \"text_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transporter uptake assays in cells expressing human THTR-1 and THTR-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin against thiamine uptake by SLC19A2 and SLC19A3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.","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":"Human transporters, with mouse orthologue comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The mouse version of this carrier does not behave like the human one.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Small-intestinal absorption","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"80ecf26d-d13d-5981-9f42-7fffd76d87d9","evidence_kind":"source_excerpt","locator":"Lines 1308-1319","start_line":1308,"end_line":1319,"excerpt":"### metformin-thtr2-species-difference\nSpecies differences in the substrate specificity of THTR-2 between the human and mouse orthologues were observed.\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 mouse version of this carrier does not behave like the human one.\norganism: Human transporters, with mouse orthologue comparison\ntissue_or_cell_type: Small-intestinal absorption\nexperimental_model: Transporter uptake assays in cells expressing human THTR-1 and THTR-2\nlimitations: In-vitro transport with a millimolar Km. The authors propose intestinal relevance; they do not measure human thiamine status.\nexposure: Metformin against thiamine uptake by SLC19A2 and SLC19A3\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/26528626.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\", \"start_char\": 0, \"end_char\": 1436, \"text_sha256\": \"67707c1e73b51b8db54bf2ffdfbb07210b877ce242d62840836f3e546dd4c6a9\"}\n[metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","model_system":"Transporter uptake assays in cells expressing human THTR-1 and THTR-2","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p26528626] Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). (2015). https://pubmed.ncbi.nlm.nih.gov/26528626/ DOI: 10.1021/acs.molpharmaceut.5b00501","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}