{"id":"e418cea9-63de-55ed-b537-fa5f753ea4d5","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:nrf2-branch-human-endothelial-insulin-signaling","predicate":"increases_in_recorded_experiment","statement":"C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"70021227-9032-5035-8719-acbdee940025","mechanism_event_label":"C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.","subject":{"id":"75149db0-02f7-5d32-8c7a-5c111d90d8ee","slug":"cyanidin-3-glucoside","display_name":"Cyanidin 3-O-beta-D-glucopyranoside","entity_type_key":"small_molecule"},"object":{"id":"b8be0b22-8c9e-5411-8cbe-df365f84cd12","slug":"human-endothelial-insulin-signaling","display_name":"IRS1/PI3K/Akt insulin-signaling readouts in human endothelium","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"70021227-9032-5035-8719-acbdee940025","stable_key":"35ec55a7-323c-5c28-979e-3bdafe9d5769:nrf2-branch-human-endothelial-insulin-signaling-event","event_type":"experimental_observation","label":"C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.","description":"**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"75149db0-02f7-5d32-8c7a-5c111d90d8ee","slug":"cyanidin-3-glucoside","display_name":"Cyanidin 3-O-beta-D-glucopyranoside","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"C3G pretreatment followed by palmitate challenge","sequence_order":0,"notes":""},{"entity":{"id":"b8be0b22-8c9e-5411-8cbe-df365f84cd12","slug":"human-endothelial-insulin-signaling","display_name":"IRS1/PI3K/Akt insulin-signaling readouts in human endothelium","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"increase","sequence_order":1,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"experimentally tested response factor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8a9c57f6-eafd-5243-afaf-d4e830939c4b","slug":"nos3","display_name":"Human endothelial nitric oxide synthase / eNOS / NOS3","entity_type_key":"protein"},"role":"NO-producing enzyme","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1d558783-9f80-531e-b09f-4c69e08ac426","slug":"irs1","display_name":"Human insulin receptor substrate 1 / IRS1","entity_type_key":"protein"},"role":"measured insulin-signaling component","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"6e161295-1c70-5d1b-8491-9d52c66bea68","slug":"palmitate","display_name":"Palmitate / hexadecanoate","entity_type_key":"small_molecule"},"role":"joint lipid challenge","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"signaling stimulus","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary indexed abstract reviewed; full methods, figures, exact doses or endpoint-specific species assignments may remain unextracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"present","comparator":"Palmitate challenge without C3G","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"cyanidin-3-glucoside","display_name":"Cyanidin 3-O-beta-D-glucopyranoside","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"signaling stimulus","comparator":"Palmitate challenge without C3G","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"insulin","display_name":"Insulin","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"challenge","comparator":"Palmitate challenge without C3G","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"palmitate","display_name":"Palmitate / hexadecanoate","entity_type_key":"small_molecule"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"C3G pretreatment followed by palmitate challenge\", \"comparator\": \"Palmitate challenge without C3G\", \"endpoint\": \"C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.\", \"effect_direction\": \"increase\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"cyanidin-3-glucoside\", \"state\": \"present\"}, {\"entity_slug\": \"palmitate\", \"state\": \"challenge\"}, {\"entity_slug\": \"insulin\", \"state\": \"signaling stimulus\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Context-specific signaling rescue; no claim of direct KEAP1 binding or dietary circulating-metabolite effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"C3G pretreatment improved IRS1/PI3K/Akt insulin signaling in palmitate-challenged human endothelial cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors. | 2017 | DOI 10.1016/j.bbalip.2016.12.008 | PMID 28011403 | https://pubmed.ncbi.nlm.nih.gov/28011403/ | https://doi.org/10.1016/j.bbalip.2016.12.008","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 72-72; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c587ccad-79da-5e39-b87f-530d34b66a32","evidence_kind":"source_excerpt","locator":"Lines 72-72","start_line":72,"end_line":72,"excerpt":"**Nrf2 dependence has been tested, but is context-specific.** C3G pretreatment in palmitate-challenged human endothelial cells improved IRS-1/PI3K/Akt-related insulin signaling and restored eNOS expression and NO release. Nrf2 silencing impaired the protective response. This is stronger than merely observing an antioxidant-gene increase, but neither direct KEAP1 binding nor the same action of circulating conjugates follows. The source's exact exposure protocol must accompany any quantitative reuse; only its accessible abstract was extracted here. [Fratantonio et al., 2017](https://pubmed.ncbi.nlm.nih.gov/28011403/).","model_system":"Palmitate-challenged HUVECs; accessible primary abstract; exact C3G dose/timing not extracted.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. 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