{"id":"9d162219-ff1b-5984-8605-efa3f48b9247","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-mouse-metformin","predicate":"reduces_tested","statement":"Imidazole-propionate pretreatment prevented the measured glucose-lowering response to metformin in mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b4bcbb76-6d6d-5acf-9fbf-73505b7f639a","mechanism_event_label":"A microbial metabolite changed a drug response in an animal model.","subject":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"object":{"id":"2fb883e9-d87d-51e1-ac51-8f669d505430","slug":"mouse-metformin-glucose-response","display_name":"Glucose-lowering response to metformin in mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b4bcbb76-6d6d-5acf-9fbf-73505b7f639a","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-imp-mouse-metformin-event","event_type":"observed_relationship","label":"A microbial metabolite changed a drug response in an animal model.","description":"Imidazole-propionate pretreatment prevented the measured glucose-lowering response to metformin in mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"06c093ed-025c-54bc-8016-6a3da64ffbf9","slug":"imidazole-propionate","display_name":"Imidazole propionate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2fb883e9-d87d-51e1-ac51-8f669d505430","slug":"mouse-metformin-glucose-response","display_name":"Glucose-lowering response to metformin in mice","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse pretreatment and metformin experiments; separate from observational human plasma data.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not evidence that histidine supplementation causes metformin failure in humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A microbial metabolite changed a drug response in an animal model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b51fa74d-4218-591d-8559-3021e3ead214","evidence_kind":"source_excerpt","locator":"Lines 346-352","start_line":346,"end_line":352,"excerpt":"## histidine-imp-mouse-metformin\nA microbial metabolite changed a drug response in an animal model.\nImidazole-propionate pretreatment prevented the measured glucose-lowering response to metformin in mice.\nModel: Mouse pretreatment and metformin experiments; separate from observational human plasma data.\nLimitations: Not evidence that histidine supplementation causes metformin failure in humans.\nEvidence access: Primary full text\nMicrobial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012","model_system":"Mouse pretreatment and metformin experiments; separate from observational human plasma data.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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