{"id":"95b8f9e1-b14e-57b0-a5d0-117a54a14d10","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-insr-loss","predicate":"silencing_diminishes_berberine_response_of","statement":"INSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c095fbfd-7261-5e7f-ad9a-9dcab5939673","mechanism_event_label":"A sensitizing signal cannot substitute for missing receptor machinery.","subject":{"id":"5cd18880-8dc7-5897-9362-7422684f5f79","slug":"insr","display_name":"Insulin receptor / INSR","entity_type_key":"protein"},"object":{"id":"47c0fabe-4562-5d87-b298-01f0092e12d4","slug":"cellular-glucose-consumption","display_name":"Cellular glucose consumption","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c095fbfd-7261-5e7f-ad9a-9dcab5939673","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-insr-loss-event","event_type":"biochemical_relationship","label":"A sensitizing signal cannot substitute for missing receptor machinery.","description":"INSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"required_signal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5cd18880-8dc7-5897-9362-7422684f5f79","slug":"insr","display_name":"Insulin receptor / INSR","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"47c0fabe-4562-5d87-b298-01f0092e12d4","slug":"cellular-glucose-consumption","display_name":"Cellular glucose consumption","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/berberine-research/19059538.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23\", \"start_char\": 0, \"end_char\": 1461, \"text_sha256\": \"70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Promoter assays, gene silencing and insulin-dependence experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Berberine with or without insulin, INSR siRNA or PKC inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Berberine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human liver cells and separate rodent experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A sensitizing signal cannot substitute for missing receptor machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Insulin receptor expression and glucose consumption","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"50a719a3-57a8-5540-b6c4-49b77c179ede","evidence_kind":"source_excerpt","locator":"Lines 506-517","start_line":506,"end_line":517,"excerpt":"### berberine-insr-loss\nINSR silencing diminished the insulin-dependent increase in glucose consumption associated with berberine-enhanced receptor expression.\nCondition category: machinery_impairment\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A sensitizing signal cannot substitute for missing receptor machinery.\norganism: Human liver cells and separate rodent experiments\ntissue_or_cell_type: Insulin receptor expression and glucose consumption\nexperimental_model: Promoter assays, gene silencing and insulin-dependence experiments\nlimitations: This insulin-dependent route does not replace insulin in insulin-deficient disease. Other models show insulin-independent routes; those observations are not discarded.\nexposure: Berberine with or without insulin, INSR siRNA or PKC inhibition\nevidence_span: {\"source_cache\": \"artifacts/berberine-research/19059538.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23\", \"start_char\": 0, \"end_char\": 1461, \"text_sha256\": \"70e22b36b13efcbb36d7f27b417fe72dc96ba2f384f01a8d037bfc2d3213ef23\"}\n[berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013","model_system":"Promoter assays, gene silencing and insulin-dependence experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berberine-p19059538] Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. (2009). https://pubmed.ncbi.nlm.nih.gov/19059538/ DOI: 10.1016/j.metabol.2008.08.013","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9bb61e1d-e5cf-5b05-a9ca-409291f7a313","stable_key":"import-7484635e-cc8f-5cd6-a978-6dc5775a7db5","title":"Berberine: metabolism, nutrient connections and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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