{"id":"c4af2df7-89f5-5f7f-9363-07073002356e","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-benfotiamine-hexosamine","predicate":"modulates_in_experiment","statement":"Benfotiamine inhibited hyperglycemia-associated hexosamine-pathway activation in the tested models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"30479e11-4693-5d20-a209-dcebf9716730","mechanism_event_label":"The intervention reduced one pathway fed by excess sugar intermediates.","subject":{"id":"bbd53f1e-98b5-50b8-8de8-b414b34b35a2","slug":"benfotiamine","display_name":"Benfotiamine","entity_type_key":"small_molecule"},"object":{"id":"6d99e289-a8ed-54a2-adb5-c142f18dd7eb","slug":"hexosamine-pathway-activity","display_name":"Hexosamine pathway activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"30479e11-4693-5d20-a209-dcebf9716730","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-benfotiamine-hexosamine-event","event_type":"biochemical_relationship","label":"The intervention reduced one pathway fed by excess sugar intermediates.","description":"Benfotiamine inhibited hyperglycemia-associated hexosamine-pathway activation in the tested models.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bf8d9a7c-ac25-524c-8839-9c8f0d759c30","slug":"glyceraldehyde-3-phosphate","display_name":"D-Glyceraldehyde 3-phosphate","entity_type_key":"small_molecule"},"role":"pathway_substrate_context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"94656f57-0fcc-555b-b7f4-fa2c14413571","slug":"fructose-6-phosphate","display_name":"D-fructose 6-phosphate","entity_type_key":"small_molecule"},"role":"pathway_substrate_context","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"13ba4537-bd0f-5817-9aae-aa255edcb5d6","slug":"diacylglycerol","display_name":"DAG","entity_type_key":"lipid"},"role":"signaling_intermediate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1919b0c7-79e7-5e3b-8b46-d666d0628ea6","slug":"rat-tkt","display_name":"Rat transketolase","entity_type_key":"protein"},"role":"enzyme_in_animal_model","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"3b376cba-b917-57f2-a34e-683638c6eebf","slug":"bovine-tkt","display_name":"Bovine transketolase","entity_type_key":"protein"},"role":"enzyme_in_cell_model","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"bbd53f1e-98b5-50b8-8de8-b414b34b35a2","slug":"benfotiamine","display_name":"Benfotiamine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"6d99e289-a8ed-54a2-adb5-c142f18dd7eb","slug":"hexosamine-pathway-activity","display_name":"Hexosamine pathway activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"High-glucose bovine endothelial cells and diabetic rat retinal experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; 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topical membership is not evidence of a direct dietary effect.\nplain_language: The intervention reduced one pathway fed by excess sugar intermediates.\norganism: Bos taurus; Rattus norvegicus\ntissue_or_cell_type: Endothelial cultures and retina\nexperimental_model: High-glucose bovine endothelial cells and diabetic rat retinal experiments.\nlimitations: Pharmacological derivative in bovine endothelial cells/diabetic rats; not proof of human dietary-thiamine benefit or direct NADPH production by transketolase.\nexposure: Pharmacological benfotiamine in high-glucose bovine endothelial cells and diabetic rat retina; not ordinary dietary thiamine.\n[b1-hammes2003] Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy (2003). https://pubmed.ncbi.nlm.nih.gov/12592403/ DOI: 10.1038/nm834","model_system":"High-glucose bovine endothelial cells and diabetic rat retinal experiments.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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