{"doi":"10.2337/db20-0553","title":"Unique Human and Mouse β-Cell Senescence-Associated Secretory Phenotype (SASP) Reveal Conserved Signaling Pathways and Heterogeneous Factors","abstract":"The aging of pancreatic β-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging β-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to β-cell failure. In this study, we defined the β-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from mouse and human senescent β-cells and a chemically induced mouse model of DNA damage capable of inducing SASP. These experiments revealed that the β-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species. Multiple SASP factors were transcriptionally upregulated in models of β-cell senescence, aging, insulin resistance, and T2D. Single-cell transcriptomic analysis of islets from an in vivo mouse model of reversible insulin resistance indicated unique and partly reversible changes in β-cell subpopulations associated with senescence. Collectively, these results demonstrate the unique secretory profile of senescent β-cells and its potential implication in health and disease.","journal":"Diabetes","year":2021,"id":155959,"datarank":1.619167909139036,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":1.0127102189638535,"self_endowment_contribution":0.6064576901751826,"citer_contribution":1.0127102189638535,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":48,"citers_with_citation_signal":42,"citers_with_endowment":42,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9478,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.14125511"]},"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":277540,"name":"Hui Pan","orcid":"0000-0001-5748-7217","position":1,"is_corresponding":false},{"id":659701,"name":"Cristian Abarca","orcid":"0000-0003-1968-2761","position":2,"is_corresponding":false},{"id":660800,"name":"Joshua Andle","orcid":null,"position":3,"is_corresponding":false},{"id":659702,"name":"Priscila Carapeto","orcid":"0000-0002-8987-9116","position":4,"is_corresponding":false},{"id":301050,"name":"Susan Bonner‐Weir","orcid":"0000-0003-4682-0656","position":5,"is_corresponding":false},{"id":631092,"name":"Cristina Aguayo‐Mazzucato","orcid":"0000-0001-5402-1382","position":6,"is_corresponding":false},{"id":659700,"name":"Ayush Midha","orcid":"0000-0002-3363-3918","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:44:08.368845Z","pmid":"33674410","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":[]}