{"doi":"10.1016/j.molmet.2021.101330","title":"Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes","abstract":"<h4>Objective</h4>The effectiveness of bariatric surgery in restoring β-cell function has been described in type-2 diabetes (T2D) patients and animal models for years, whereas the mechanistic underpinnings are largely unknown. The possibility of vertical sleeve gastrectomy (VSG) to rescue far-progressed, clinically-relevant T2D and to promote β-cell recovery has not been investigated on a single-cell level. Nevertheless, characterization of the heterogeneity and functional states of β-cells after VSG is a fundamental step to understand mechanisms of glycaemic recovery and to ultimately develop alternative, less-invasive therapies.<h4>Methods</h4>We performed VSG in late-stage diabetic db/db mice and analyzed the islet transcriptome using single-cell RNA sequencing (scRNA-seq). Immunohistochemical analyses and quantification of β-cell area and proliferation complement our findings from scRNA-seq.<h4>Results</h4>We report that VSG was superior to calorie restriction in late-stage T2D and rapidly restored normoglycaemia in morbidly obese and overt diabetic db/db mice. Single-cell profiling of islets of Langerhans showed that VSG induced distinct, intrinsic changes in the β-cell transcriptome, but not in that of α-, δ-, and PP-cells. VSG triggered fast β-cell redifferentiation and functional improvement within only two weeks of intervention, which is not seen upon calorie restriction. Furthermore, VSG expanded β-cell area by means of redifferentiation and by creating a proliferation competent β-cell state.<h4>Conclusion</h4>Collectively, our study reveals the superiority of VSG in the remission of far-progressed T2D and presents paths of β-cell regeneration and molecular pathways underlying the glycaemic benefits of VSG.","journal":"Molecular Metabolism","year":2021,"id":7774,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0465,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31685,"name":"Subarna Palit","orcid":null,"position":1,"is_corresponding":false},{"id":70425,"name":"Kerstin Stemmer","orcid":"0000-0002-7526-2326","position":2,"is_corresponding":false},{"id":70426,"name":"Tobias Greisle","orcid":"0000-0002-3885-4939","position":3,"is_corresponding":false},{"id":6097,"name":"Michael Sterr","orcid":null,"position":4,"is_corresponding":false},{"id":34882,"name":"Ciro Salinno","orcid":"0000-0003-4364-3236","position":5,"is_corresponding":false},{"id":18912,"name":"Aimée Bastidas-Ponce","orcid":"0000-0002-3117-3591","position":6,"is_corresponding":false},{"id":66094,"name":"Annette Feuchtinger","orcid":"0000-0003-4324-2547","position":7,"is_corresponding":false},{"id":6099,"name":"Anika Böttcher","orcid":"0000-0001-5473-3136","position":8,"is_corresponding":false},{"id":6100,"name":"Ansarullah","orcid":null,"position":9,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":10,"is_corresponding":false},{"id":2920,"name":"Heiko Lickert","orcid":"0000-0002-4597-8825","position":11,"is_corresponding":false},{"id":70427,"name":"Md Ansarullah","orcid":null,"position":12,"is_corresponding":false},{"id":36048,"name":"Lena Oppenländer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}