{"id":"a6dc1a75-ada6-5b67-9c11-b2c87c87dc7b","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-adipocyte-insr-redox","predicate":"increases","statement":"Lipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"930ef8bd-0af6-5427-814b-f25ca0ff15af","mechanism_event_label":"A local oxidant signal accompanied insulin-receptor activation.","subject":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"object":{"id":"8fe041ac-698e-589b-bdb9-b3470440fa8e","slug":"mouse-insulin-receptor-phosphorylation","display_name":"Mouse adipocyte insulin-receptor autophosphorylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"930ef8bd-0af6-5427-814b-f25ca0ff15af","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-adipocyte-insr-redox-event","event_type":"biochemical_relationship","label":"A local oxidant signal accompanied insulin-receptor activation.","description":"Lipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"de559400-6a45-5ef3-80e3-ebe96ef4b83a","slug":"mouse-insr","display_name":"Mouse insulin receptor / Insr","entity_type_key":"protein"},"role":"receptor","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":"8fe041ac-698e-589b-bdb9-b3470440fa8e","slug":"mouse-insulin-receptor-phosphorylation","display_name":"Mouse adipocyte insulin-receptor autophosphorylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/12948866.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9\", \"start_char\": 0, \"end_char\": 1489, \"text_sha256\": \"0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Protein-thiol, phosphorylation and glucose-uptake assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Alpha-lipoic-acid stimulation with redox/thiol inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings.","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":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A local oxidant signal accompanied insulin-receptor activation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"3T3-L1 adipocytes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2953b882-3b97-5fcc-a6af-c862e8d9acc9","evidence_kind":"source_excerpt","locator":"Lines 936-947","start_line":936,"end_line":947,"excerpt":"### ala-adipocyte-insr-redox\nLipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A local oxidant signal accompanied insulin-receptor activation.\norganism: Mouse\ntissue_or_cell_type: 3T3-L1 adipocytes\nexperimental_model: Protein-thiol, phosphorylation and glucose-uptake assays\nlimitations: Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings.\nexposure: Alpha-lipoic-acid stimulation with redox/thiol inhibitors\nevidence_span: {\"source_cache\": \"artifacts/ala-research/12948866.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9\", \"start_char\": 0, \"end_char\": 1489, \"text_sha256\": \"0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9\"}\n[ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. 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