{"id":"6760f818-c088-5f2e-8b5b-61f867cfccfa","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-lkb1-ampk-axis","predicate":"activates","statement":"Deletion of LKB1 in adult mouse liver resulted in a nearly complete loss of AMPK activity, with hyperglycaemia and increased gluconeogenic and lipogenic gene expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"2abeac6b-c4c7-561e-8e39-e135cee05360","mechanism_event_label":"The upstream kinase is what turns the energy sensor on in the liver.","subject":{"id":"718da13a-06a0-58c2-ab52-900ab07f9bf3","slug":"stk11","display_name":"Human liver kinase B1 / STK11","entity_type_key":"protein"},"object":{"id":"8128eec0-61cc-51ef-8d4e-5ec9678e8dfa","slug":"ampk-complexes","display_name":"AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"2abeac6b-c4c7-561e-8e39-e135cee05360","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-lkb1-ampk-axis-event","event_type":"biochemical_relationship","label":"The upstream kinase is what turns the energy sensor on in the liver.","description":"Deletion of LKB1 in adult mouse liver resulted in a nearly complete loss of AMPK activity, with hyperglycaemia and increased gluconeogenic and lipogenic gene expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"460cb40a-b169-5f1c-8f93-74ceb3368bad","slug":"gluconeogenic-gene-expression","display_name":"Hepatic gluconeogenic gene expression","entity_type_key":"cellular_process"},"role":"downstream_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"718da13a-06a0-58c2-ab52-900ab07f9bf3","slug":"stk11","display_name":"Human liver kinase B1 / STK11","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8128eec0-61cc-51ef-8d4e-5ec9678e8dfa","slug":"ampk-complexes","display_name":"AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/16308421.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4\", \"start_char\": 0, \"end_char\": 1103, \"text_sha256\": \"e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Liver-specific LKB1 deletion in adult mice with adenoviral TORC2 knockdown","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin in LKB1-deficient livers","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A genetic requirement in this model. 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The same year’s consensus was later challenged by AMPK-independent findings recorded in this collection.\nexposure: Metformin in LKB1-deficient livers\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/16308421.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4\", \"start_char\": 0, \"end_char\": 1103, \"text_sha256\": \"e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4\"}\n[metformin-p16308421] The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. (2005). https://pubmed.ncbi.nlm.nih.gov/16308421/ DOI: 10.1126/science.1120781","model_system":"Liver-specific LKB1 deletion in adult mice with adenoviral TORC2 knockdown","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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