{"id":"cea24fa5-7a23-5460-8c3a-cfef995dd16a","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-insr-expression","predicate":"increases_expression_of","statement":"Berberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2b3ff410-65ca-5356-ac14-d3888883094a","mechanism_event_label":"The cells increased the machinery that receives an insulin signal.","subject":{"id":"7bbe0633-b2f1-510f-adc0-3c4d0ddad05d","slug":"berberine","display_name":"Berberine","entity_type_key":"small_molecule"},"object":{"id":"5cd18880-8dc7-5897-9362-7422684f5f79","slug":"insr","display_name":"Insulin receptor / INSR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2b3ff410-65ca-5356-ac14-d3888883094a","stable_key":"7484635e-cc8f-5cd6-a978-6dc5775a7db5:berberine-insr-expression-event","event_type":"biochemical_relationship","label":"The cells increased the machinery that receives an insulin signal.","description":"Berberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f1d300e9-ab88-5173-af8c-b5f7bde1c334","slug":"protein-kinase-c-family","display_name":"Protein kinase C family","entity_type_key":"protein_family"},"role":"upstream_signaling_family","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":"subject","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":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"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":"The cells increased the machinery that receives an insulin signal.","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}],"evidence":[{"id":"b5eb90fe-bc74-52c3-8f44-410bd72a7d64","evidence_kind":"source_excerpt","locator":"Lines 493-504","start_line":493,"end_line":504,"excerpt":"### berberine-insr-expression\nBerberine increased INSR mRNA and protein in human liver cells through PKC-dependent promoter activation.\nCondition category: normal\nnutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cells increased the machinery that receives an insulin signal.\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. Not publisher full text.","file_path":"","sha256":"2f376a035ae79c93e62e2ea4a8d5385643bf16553f108d12b6a80c89e6d41f4c","revision_id":"2a099429-1c4a-55be-aa2c-0565d08bda80","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}