{"doi":"10.1172/jci164185","title":"The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis","abstract":"Glucose homeostasis can be improved after bariatric surgery, which alters bile flow and stimulates gut hormone secretion, particularly FGF15/19. FGFR1 expression in AGRP-expressing cells is required for bile acids' ability to improve glucose control. We show that the mouse Agrp gene has 3 promoter/enhancer regions that direct transcription of each of their own AGRP transcripts. One of these Agrp promoters/enhancers, Agrp-B, is regulated by bile acids. We generated an Agrp-B knockin FLP/knockout allele. AGRP-B-expressing cells are found in endocrine cells of the pars tuberalis and coexpress diacylglycerol lipase B - an endocannabinoid biosynthetic enzyme - distinct from pars tuberalis thyrotropes. AGRP-B expression is also found in the folliculostellate cells of the pituitary's anterior lobe. Mice without AGRP-B were protected from glucose intolerance induced by high-fat feeding but not from excess weight gain. Chemogenetic inhibition of AGRP-B cells improved glucose tolerance by enhancing glucose-stimulated insulin secretion. Inhibition of the AGRP-B cells also caused weight loss. The improved glucose tolerance and reduced body weight persisted up to 6 weeks after cessation of the DREADD-mediated inhibition, suggesting the presence of a biological switch for glucose homeostasis that is regulated by long-term stability of food availability.","journal":"Journal of Clinical Investigation","year":2023,"id":357634,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1107883,"name":"Bruno Ifebi","orcid":null,"position":1,"is_corresponding":false},{"id":1107414,"name":"Fred M. Johnson","orcid":"0000-0002-1117-5709","position":2,"is_corresponding":false},{"id":1107415,"name":"Alison Xu","orcid":"0000-0002-9034-3765","position":3,"is_corresponding":false},{"id":1068946,"name":"Jacquelin Ho","orcid":"0000-0003-2737-0231","position":4,"is_corresponding":false},{"id":280587,"name":"Yunlei Yang","orcid":"0000-0002-7623-6680","position":5,"is_corresponding":false},{"id":321278,"name":"Gary J. Schwartz","orcid":"0000-0003-0446-5553","position":6,"is_corresponding":false},{"id":321279,"name":"Young‐Hwan Jo","orcid":"0000-0001-6939-8000","position":7,"is_corresponding":false},{"id":321277,"name":"Streamson C. Chua","orcid":"0000-0002-9437-9925","position":8,"is_corresponding":false},{"id":322178,"name":"Shun-Mei Liu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"36787185","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}