{"doi":"10.1101/2022.04.06.487366","title":"Beta-cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood","abstract":"ABSTRACT Puberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children insulin resistance persists leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how they are affected by the metabolic status, have not been investigated. Here we show that puberty is associated with a transient increase in β-cell proliferation in rats and humans of both sexes. In rats, β-cell proliferation correlated with a rise in growth hormone (GH) levels. Serum from pubertal rats and humans promoted β-cell proliferation, suggesting the implication of a circulating factor. In pubertal rat islets, expression of genes of the GH/serotonin (5-HT) pathway underwent changes consistent with proliferative effect. Inhibition of the pro-proliferative 5-HT receptor isoform HTR2b blocked the increase in β-cell proliferation in pubertal islets ex vivo and in vivo. Peri-pubertal metabolic stress blunted β-cell proliferation during puberty and led to altered glucose homeostasis later in life. This study identifies a role of GH/GHR/5-HT/HTR2b signaling in the control of β-cell mass expansion during puberty and a mechanistic link between pubertal obesity and the risk of developing type 2 diabetes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303203,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":879161,"name":"Mélanie Éthier","orcid":null,"position":1,"is_corresponding":false},{"id":879162,"name":"Grace Fergusson","orcid":null,"position":2,"is_corresponding":false},{"id":577852,"name":"Caroline Tremblay","orcid":null,"position":3,"is_corresponding":false},{"id":879160,"name":"Clara Goubault","orcid":null,"position":4,"is_corresponding":false},{"id":879163,"name":"Marie Baltz","orcid":null,"position":5,"is_corresponding":false},{"id":879164,"name":"Dorothée Dal Soglio","orcid":null,"position":6,"is_corresponding":false},{"id":878580,"name":"J. Ghislain","orcid":"0000-0001-8254-8245","position":7,"is_corresponding":false},{"id":576873,"name":"Vincent Poitout","orcid":"0000-0002-6555-5053","position":8,"is_corresponding":false},{"id":828924,"name":"Anne‐Laure Castell","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"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":[]}