{"id":"d3617e48-2f36-5d34-878b-7bfe36604cd8","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-beta-chronic-desensitization","predicate":"desensitizes","statement":"Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2ff1d7eb-8791-5de7-873c-f7087acc78a8","mechanism_event_label":"A strong acute response need not persist after prolonged exposure.","subject":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"object":{"id":"430b732c-3469-5fe8-8fde-0686d6900abd","slug":"rat-brin-alanine-insulin","display_name":"Alanine-stimulated insulin secretion in BRIN-BD11 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2ff1d7eb-8791-5de7-873c-f7087acc78a8","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-beta-chronic-desensitization-event","event_type":"observed_relationship","label":"A strong acute response need not persist after prolonged exposure.","description":"Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"430b732c-3469-5fe8-8fde-0686d6900abd","slug":"rat-brin-alanine-insulin","display_name":"Alanine-stimulated insulin secretion in BRIN-BD11 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8ae7848b-f172-5e09-8acf-5ca914907b0b","slug":"glucose","display_name":"D-glucose","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"bbdfd11c-42dd-520e-8a1f-7fe3d19e3e0e","slug":"alpha-ketoisocaproate","display_name":"4-Methyl-2-oxopentanoate / alpha-ketoisocaproate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat BRIN-BD11 culture, washout and rechallenge experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A strong acute response need not persist after prolonged exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"605238f7-4f7d-51b8-8c7b-d4eaeb5b561b","evidence_kind":"source_excerpt","locator":"Lines 400-406","start_line":400,"end_line":406,"excerpt":"## alanine-beta-chronic-desensitization\nA strong acute response need not persist after prolonged exposure.\nProlonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness.\nModel: Rat BRIN-BD11 culture, washout and rechallenge experiments.\nLimitations: Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.\nEvidence access: Primary abstract\nProlonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138","model_system":"Rat BRIN-BD11 culture, washout and rechallenge experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"01c5554c-a8ba-5c86-9b01-a0fa1a886cdb","stable_key":"import-10aa417f-4b03-599f-a453-4aa09edeb27c","title":"L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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