{"id":"6bbd5abb-e8eb-5d14-b84d-eaa1244fd822","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-myotube-pi3k","predicate":"engages_tested","statement":"Pharmacological experiments implicated PI3K, while mTOR inhibition did not account for the isoleucine glucose-uptake response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6ed26cd4-ae19-5a1c-b785-48462cd64536","mechanism_event_label":"This effect was not simply the familiar mTOR protein-growth pathway.","subject":{"id":"c85b327e-f132-5d9a-8e4b-c2976fcc0373","slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"},"object":{"id":"0ac21c32-b3f2-5dfe-aaaf-8dc48649bf73","slug":"mouse-c2c12-pi3k-sensitive-glucose-response","display_name":"PI3K-sensitive glucose response in mouse C2C12 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6ed26cd4-ae19-5a1c-b785-48462cd64536","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-myotube-pi3k-event","event_type":"observed_relationship","label":"This effect was not simply the familiar mTOR protein-growth pathway.","description":"Pharmacological experiments implicated PI3K, while mTOR inhibition did not account for the isoleucine glucose-uptake response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c85b327e-f132-5d9a-8e4b-c2976fcc0373","slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0ac21c32-b3f2-5dfe-aaaf-8dc48649bf73","slug":"mouse-c2c12-pi3k-sensitive-glucose-response","display_name":"PI3K-sensitive glucose response in mouse C2C12 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9f025af3-f039-517f-908b-4af6fc65415e","slug":"mtorc1","display_name":"Mechanistic target of rapamycin complex 1","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse C2C12 myotubes; pathway inhibitor experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inhibitor evidence does not establish direct binding of isoleucine to PI3K or identify the upstream sensor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"This effect was not simply the familiar mTOR protein-growth pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14651987/ · DOI 10.1016/j.bbrc.2003.11.039","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a9300f45-74b6-516a-90b7-5a282419a5df","evidence_kind":"source_excerpt","locator":"Lines 354-360","start_line":354,"end_line":360,"excerpt":"## isoleucine-myotube-pi3k\nThis effect was not simply the familiar mTOR protein-growth pathway.\nPharmacological experiments implicated PI3K, while mTOR inhibition did not account for the isoleucine glucose-uptake response.\nModel: Mouse C2C12 myotubes; pathway inhibitor experiments.\nLimitations: Inhibitor evidence does not establish direct binding of isoleucine to PI3K or identify the upstream sensor.\nEvidence access: Primary abstract\nIsoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14651987/ · DOI 10.1016/j.bbrc.2003.11.039","model_system":"Mouse C2C12 myotubes; pathway inhibitor experiments.","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":"4b00f118-00fd-5cef-be97-13125eb958e9","stable_key":"import-09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2","title":"L-Isoleucine: transport, translation, catabolism 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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