{"id":"407fb305-6515-517c-8009-2099f205e956","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-the-islet-signals-with-gaba","predicate":"inhibits","statement":"The inhibitory neurotransmitter GABA is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system and co-localizes with insulin in pancreatic beta cells, and we describe a mechanism whereby GABA co-secreted with insulin from beta cells may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABA-A receptor chloride channels in alpha 2 cells, providing a model for feedback regulation of glucagon release which may be of significance for understanding the hypersecretion of glucagon frequently associated with diabetes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f6524a12-368a-50be-99da-a2dbd187365a","mechanism_event_label":"The cells that release insulin release GABA with it, and that is part of how a meal switches off the opposing hormone.","subject":{"id":"d5b98fa8-0612-5a5a-aa3c-6cfd8ff88867","slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"},"object":{"id":"ac698f9b-f356-5545-98b7-27ab3574ae41","slug":"glucagon-secretion","display_name":"Glucagon secretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f6524a12-368a-50be-99da-a2dbd187365a","stable_key":"1b599eb7-b22a-5fda-bcf0-9d92b5ae1311:gb-the-islet-signals-with-gaba-event","event_type":"biochemical_relationship","label":"The cells that release insulin release GABA with it, and that is part of how a meal switches off the opposing hormone.","description":"The inhibitory neurotransmitter GABA is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system and co-localizes with insulin in pancreatic beta cells, and we describe a mechanism whereby GABA co-secreted with insulin from beta cells may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABA-A receptor chloride channels in alpha 2 cells, providing a model for feedback regulation of glucagon release which may be of significance for understanding the hypersecretion of glucagon frequently associated with diabetes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"66709f33-8eeb-5618-b262-023a13db02ad","slug":"islet-beta-cell","display_name":"Pancreatic islet beta cell","entity_type_key":"cell_type"},"role":"source_cell","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cc38d77f-460d-58f8-b3b9-48f85c967403","slug":"islet-alpha-cell","display_name":"Pancreatic islet alpha cell","entity_type_key":"cell_type"},"role":"target_cell","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d7ab69c0-cd7d-587c-b315-47af56493182","slug":"insulin","display_name":"Insulin","entity_type_key":"protein"},"role":"co_released_hormone","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5e42971b-427f-5b32-968b-870b347135ab","slug":"gaba-a-receptors","display_name":"GABA-A receptor anion channels","entity_type_key":"protein_family"},"role":"target_receptor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d5b98fa8-0612-5a5a-aa3c-6cfd8ff88867","slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"ac698f9b-f356-5545-98b7-27ab3574ae41","slug":"glucagon-secretion","display_name":"Glucagon secretion","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/gaba-research/2550826.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94\", \"start_char\": 0, \"end_char\": 1225, \"text_sha256\": \"9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Electrophysiology of pancreatic alpha 2 cells with glucose and GABA","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"GABA co-secreted with insulin from beta cells, acting on GABA-A receptor chloride channels in alpha 2 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An early electrophysiological model. It proposes that GABA mediates part of the effect of glucose rather than demonstrating the whole of it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in.","comparator":null,"unit":null,"notes":"","entity":{"slug":"gaba","display_name":"Gamma-aminobutyric acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Guinea pig and rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The cells that release insulin release GABA with it, and that is part of how a meal switches off the opposing hormone.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gb-p2550826] Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. 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It proposes that GABA mediates part of the effect of glucose rather than demonstrating the whole of it.\nexposure: GABA co-secreted with insulin from beta cells, acting on GABA-A receptor chloride channels in alpha 2 cells\nevidence_span: {\"source_cache\": \"artifacts/gaba-research/2550826.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94\", \"start_char\": 0, \"end_char\": 1225, \"text_sha256\": \"9062539804213a1ccf427b75c8f6d262b151e22464cd6b7c84640f222f7dea94\"}\n[gb-p2550826] Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. (1989). https://pubmed.ncbi.nlm.nih.gov/2550826/ DOI: 10.1038/341233a0","model_system":"Electrophysiology of pancreatic alpha 2 cells with glucose and GABA","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [gb-p2550826] Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. 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