{"doi":"10.1016/j.bpc.2024.107201","title":"The processing intermediate of human amylin, pro-amylin(1–48), has in vivo and in vitro bioactivity","abstract":"Amylin is released by pancreatic beta-cells in response to a meal and its major soluble mature form (37 amino acid-peptide) produces its biological effects by activating amylin receptors. Amylin is derived from larger propeptides that are processed within the synthesizing beta-cell. There are suggestions that a partially processed form, pro-amylin(1-48) is also secreted. We tested the hypothesis that pro-amylin(1-48) has biological activity and that human pro-amylin(1-48) may also form toxic pre-amyloid species. Amyloid formation, the ability to cross-seed and in vitro toxicity were similar between human pro-amylin(1-48) and amylin. Human pro-amylin(1-48) was active at amylin-responsive receptors, though its potency was reduced at rat, but not human amylin receptors. Pro-amylin(1-48) was able to promote anorexia by activating neurons of the area postrema, amylin's primary site of action, indicating that amylin can tolerate significant additions at the N-terminus without losing bioactivity. Our studies help to shed light on the possible roles of pro-amylin(1-48) which may be relevant for the development of future amylin-based drugs.","journal":"Biophysical Chemistry","year":2024,"id":439747,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"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":920935,"name":"Christelle Le Foll","orcid":"0000-0002-6677-5488","position":1,"is_corresponding":false},{"id":1251045,"name":"Christina N. Boyle","orcid":"0000-0002-1060-2529","position":2,"is_corresponding":false},{"id":891699,"name":"Michael L. Garelja","orcid":"0000-0001-5332-1236","position":3,"is_corresponding":false},{"id":394956,"name":"Alexander Zhyvoloup","orcid":"0000-0003-2450-8979","position":4,"is_corresponding":false},{"id":1251046,"name":"Matthew E.T. Miller","orcid":"0000-0001-9599-8982","position":5,"is_corresponding":false},{"id":328299,"name":"Debbie L. Hay","orcid":"0000-0002-9558-5122","position":6,"is_corresponding":false},{"id":394960,"name":"Daniel P. Raleigh","orcid":"0000-0003-3248-7493","position":7,"is_corresponding":false},{"id":664994,"name":"Thomas A. Lutz","orcid":"0000-0002-5056-8548","position":8,"is_corresponding":false},{"id":176552,"name":"Giulia Mazzini","orcid":"0000-0001-7695-2938","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:00:52.633010Z","pmid":"38452520","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":[]}