{"doi":"10.2337/figshare.20080700","title":"Heterogeneous development of β-cell populations in diabetes-resistant and  susceptible mice","abstract":"<jats:p>&lt;p&gt;  &lt;/p&gt;\n&lt;p&gt;Progressive dysfunction and failure of insulin-releasing β-cells is a hallmark of type 2 diabetes (T2D). To study mechanisms of β-cell loss in T2D, we performed islet single-cell RNA-sequencing of two obese mouse strains differing in their diabetes susceptibility. On a control diet, we identified six β-cell clusters with similar abundance in both strains. However, after feeding a diabetogenic diet for two days, β-cell cluster composition markedly differed between strains. Islets of diabetes-resistant mice developed into a protective β-cell cluster (&lt;em&gt;Beta4&lt;/em&gt;), whereas those of diabetes-prone mice progressed towards stress-related clusters with a strikingly different expression pattern. Interestingly, the protective cluster showed indications of reduced β-cell identity, such as downregulation of GLUT2, GLP1R and MafA, and &lt;em&gt;in-vitro&lt;/em&gt; knockdown of GLUT2 in β-cells to mimick its phenotype decreased stress response and apoptosis. This might explain enhanced β-cell survival of diabetes-resistant islets. In contrast, β-cells of diabetes-prone mice responded with expression changes indicating metabolic pressure and ER stress, presumably leading to later β-cell loss. In conclusion, failure of diabetes-prone mice to adapt gene expression towards a more dedifferentiated state in response to rising blood glucose levels leads to β-cell failure and diabetes development.&lt;/p&gt;</jats:p>","journal":null,"year":2022,"id":1413,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-06-30","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":17037,"name":"Thilo Speckmann","orcid":"0000-0001-7265-0879","position":1,"is_corresponding":false},{"id":17038,"name":"Mandy Stadion","orcid":null,"position":2,"is_corresponding":false},{"id":17039,"name":"Erika Zuljan","orcid":null,"position":3,"is_corresponding":false},{"id":17040,"name":"Heja Aga","orcid":"0000-0002-8765-9881","position":4,"is_corresponding":false},{"id":6097,"name":"Michael Sterr","orcid":null,"position":5,"is_corresponding":false},{"id":3572,"name":"Maren Büttner","orcid":"0000-0002-6189-3792","position":6,"is_corresponding":false},{"id":17041,"name":"Patricia Martinez Santos","orcid":null,"position":7,"is_corresponding":false},{"id":17042,"name":"Markus Jähnert","orcid":"0000-0001-6459-7318","position":8,"is_corresponding":false},{"id":17043,"name":"Stefan R. Bornstein","orcid":"0000-0002-5211-2536","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":17044,"name":"Annette Schürmann","orcid":"0000-0002-4113-4377","position":12,"is_corresponding":false},{"id":17036,"name":"Pascal Gottmann","orcid":"0000-0002-9791-783X","position":0,"is_corresponding":true}],"reference_count":0,"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":[]}