{"id":"b3e1b4ba-56c9-5462-b024-45851a8bb943","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-insulin-trpm6-surface-regulation","predicate":"increases","statement":"Insulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"750eaed4-9d87-55ce-b7ee-31db6434b601","mechanism_event_label":"Insulin can affect the magnesium entry machinery as well as glucose metabolism.","subject":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"object":{"id":"7b8386d7-b9ba-58aa-80e3-12a0f5287a1e","slug":"trpm6-cell-surface-abundance","display_name":"TRPM6 abundance at the cell surface","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"750eaed4-9d87-55ce-b7ee-31db6434b601","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-insulin-trpm6-surface-regulation-event","event_type":"biochemical_relationship","label":"Insulin can affect the magnesium entry machinery as well as glucose metabolism.","description":"Insulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"877a2fb0-067c-51ca-afea-f63ff16affc8","slug":"trpm6","display_name":"TRPM6","entity_type_key":"protein"},"role":"regulated_channel","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"359979da-c958-50bf-b2f7-9f15e177fa5d","slug":"pi3k-family","display_name":"Phosphoinositide 3-kinase family","entity_type_key":"protein_family"},"role":"pathway_dependency","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8a96d7c7-d28d-5615-94a7-3c397bed8f9d","slug":"rac1","display_name":"RAC1","entity_type_key":"protein"},"role":"pathway_dependency","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"channel_substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"7b8386d7-b9ba-58aa-80e3-12a0f5287a1e","slug":"trpm6-cell-surface-abundance","display_name":"TRPM6 abundance at the cell surface","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Expression-cell electrophysiology and surface fluorescence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Insulin can affect the magnesium entry machinery as well as glucose metabolism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"TRPM6-expressing cells; plasma membrane","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ef37a046-c935-52ad-9330-a13668cae87e","evidence_kind":"source_excerpt","locator":"Lines 1527-1537","start_line":1527,"end_line":1537,"excerpt":"### mg-insulin-trpm6-surface-regulation\nInsulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway.\nCondition category: normal\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Insulin can affect the magnesium entry machinery as well as glucose metabolism.\norganism: Homo sapiens\ntissue_or_cell_type: TRPM6-expressing cells; plasma membrane\nexperimental_model: Expression-cell electrophysiology and surface fluorescence.\nlimitations: Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven.\ncross_nutrient: Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings.\n[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","model_system":"Expression-cell electrophysiology and surface fluorescence.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (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":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}