{"id":"5abc01cf-e1b5-5e64-b22f-f44818c64b74","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-myotube-pi3k-akt","predicate":"activates","statement":"Lipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"086351bb-81b3-5361-a342-d5c53146dcf0","mechanism_event_label":"A high experimental exposure engaged part of the insulin-signaling pathway.","subject":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"object":{"id":"b10814b4-df01-5076-a136-a27836193867","slug":"rat-pi3k-enzymes","display_name":"Rat phosphoinositide 3-kinase enzymes","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"086351bb-81b3-5361-a342-d5c53146dcf0","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-myotube-pi3k-akt-event","event_type":"biochemical_relationship","label":"A high experimental exposure engaged part of the insulin-signaling pathway.","description":"Lipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9597cc7c-6935-5693-b3d2-468213d4f636","slug":"rat-akt1","display_name":"Rat Akt1","entity_type_key":"protein"},"role":"downstream_kinase","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b10814b4-df01-5076-a136-a27836193867","slug":"rat-pi3k-enzymes","display_name":"Rat phosphoinositide 3-kinase enzymes","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/11375349.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111\", \"start_char\": 0, \"end_char\": 1734, \"text_sha256\": \"971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Signaling, transporter localization and glucose-uptake assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2.5 mmol/L lipoic acid; PI3K and p38 inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A high experimental exposure engaged part of the insulin-signaling pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"L6 myotubes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bc084e0d-ae74-53f5-b7fd-ef409292b72e","evidence_kind":"source_excerpt","locator":"Lines 897-908","start_line":897,"end_line":908,"excerpt":"### ala-myotube-pi3k-akt\nLipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A high experimental exposure engaged part of the insulin-signaling pathway.\norganism: Rat\ntissue_or_cell_type: L6 myotubes\nexperimental_model: Signaling, transporter localization and glucose-uptake assays\nlimitations: High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose.\nexposure: 2.5 mmol/L lipoic acid; PI3K and p38 inhibitors\nevidence_span: {\"source_cache\": \"artifacts/ala-research/11375349.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111\", \"start_char\": 0, \"end_char\": 1734, \"text_sha256\": \"971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111\"}\n[ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464","model_system":"Signaling, transporter localization and glucose-uptake assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. 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