{"doi":"10.3390/ijms22083950","title":"β Cell GHS-R Regulates Insulin Secretion and Sensitivity","abstract":"Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFP mice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in β and α cells. We then generated β-cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT;Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT;Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT;Ghsrf/f mice showed lower fasting blood glucose and insulin; reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT;Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT;Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic β and α cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, β cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.","journal":"International Journal of Molecular Sciences","year":2021,"id":187770,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":747423,"name":"Chia‐Shan Wu","orcid":"0000-0002-6034-939X","position":1,"is_corresponding":false},{"id":747424,"name":"Daniel Villarreal","orcid":"0000-0002-9719-4870","position":2,"is_corresponding":false},{"id":747425,"name":"Jong Han Lee","orcid":"0000-0002-5614-1537","position":3,"is_corresponding":false},{"id":747426,"name":"Hye Won Han","orcid":"0000-0002-9839-0996","position":4,"is_corresponding":false},{"id":232834,"name":"Akhilesh K. Gaharwar","orcid":"0000-0002-0284-0201","position":5,"is_corresponding":false},{"id":747427,"name":"Yanan Tian","orcid":"0000-0002-9946-2998","position":6,"is_corresponding":false},{"id":483115,"name":"Wenxian Fu","orcid":"0000-0003-0684-8929","position":7,"is_corresponding":false},{"id":695315,"name":"Shaodong Guo","orcid":"0000-0001-5126-731X","position":8,"is_corresponding":false},{"id":120202,"name":"Roy G. Smith","orcid":null,"position":9,"is_corresponding":false},{"id":484733,"name":"Yuxiang Sun","orcid":"0000-0002-6656-3733","position":10,"is_corresponding":false},{"id":747909,"name":"Geetali Pradhan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:48:55.420619Z","pmid":"33920473","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":[]}