{"doi":"10.1172/jci182325","title":"Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits","abstract":"Following a meal, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), the 2 major incretins promoting insulin release, are secreted from specialized enteroendocrine cells (L and K cells, respectively). Although GIP is the dominant incretin in humans, the detailed molecular mechanisms governing its release remain to be explored. GIP secretion is regulated by the activity of G protein-coupled receptors (GPCRs) expressed by K cells. GPCRs couple to 1 or more specific classes of heterotrimeric G proteins. In the present study, we focused on the potential metabolic roles of K cell Gs. First, we generated a mouse model that allowed us to selectively stimulate K cell Gs signaling. Second, we generated a mouse strain harboring an inactivating mutation of Gnas, the gene encoding the α-subunit of Gs, selectively in K cells. Metabolic phenotyping studies showed that acute or chronic stimulation of K cell Gs signaling greatly improved impaired glucose homeostasis in obese mice and in a mouse model of type 2 diabetes, due to enhanced GIP secretion. In contrast, K cell-specific Gnas-KO mice displayed markedly reduced plasma GIP levels. These data strongly suggest that strategies aimed at enhancing K cell Gs signaling may prove useful for the treatment of diabetes and related metabolic diseases.","journal":"Journal of Clinical Investigation","year":2024,"id":458646,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707630,"name":"Liu Liu","orcid":"0000-0002-8751-7103","position":1,"is_corresponding":false},{"id":464125,"name":"Yinghong Cui","orcid":"0000-0002-9889-6655","position":2,"is_corresponding":false},{"id":1284907,"name":"Оксана Гаврилова","orcid":"0000-0003-0014-8374","position":3,"is_corresponding":false},{"id":478175,"name":"Huiyan Lü","orcid":null,"position":4,"is_corresponding":false},{"id":1284908,"name":"Min Chen","orcid":"0000-0001-8645-5193","position":5,"is_corresponding":false},{"id":292018,"name":"Lee S. Weinstein","orcid":"0000-0002-1899-5152","position":6,"is_corresponding":false},{"id":226902,"name":"Jonathan E. Campbell","orcid":"0000-0003-4358-6331","position":7,"is_corresponding":false},{"id":832254,"name":"Jo E. Lewis","orcid":"0000-0002-5722-6778","position":8,"is_corresponding":false},{"id":325589,"name":"Fiona M. Gribble","orcid":"0000-0002-4232-2898","position":9,"is_corresponding":false},{"id":260268,"name":"Frank Reimann","orcid":"0000-0001-9399-6377","position":10,"is_corresponding":false},{"id":275781,"name":"Jürgen Wess","orcid":"0000-0003-0818-1232","position":11,"is_corresponding":false},{"id":707305,"name":"Antwi‐Boasiako Oteng","orcid":"0000-0002-4879-065X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:03:50.608887Z","pmid":"39436694","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":[]}