{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Roy G"],"funding":["National Center for Advancing Translational Sciences","BLRD VA","Indiana University","Wisconsin Alumni Research Foundation","NCATS NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","NIA NIH HHS","University of Wisconsin-Madison","National Institutes of Health","National Institute of General Medical Sciences","National Institute on Aging","Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison","NIDDK NIH HHS","Congenital Hyperinsulinism International","Indiana Clinical and Translational Sciences Institute","National Cancer Institute","School of Medicine, Indiana University","American Diabetes Association","NCI NIH HHS","U.S. Department of Veterans Affairs","NIGMS NIH HHS"],"pagination":["115834"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12266945"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(6)"],"pubmed_abstract":["β cells are dysfunctional in type 2 diabetes (T2D) and congenital hyperinsulinism (HI), but the mechanisms linking hypersecretion to β cell failure are poorly understood. Here, we use proteomics and functional assays in human and mouse β cell lines to identify VDAC1 as a target for the small molecule hypersecretion inducer SW016789. By enhancing membrane depolarization, SW016789 acutely increases Ca<sup>2+</sup> influx, eventually driving β cell dysfunction. Time-course transcriptomics analysis reveals a distinct hypersecretory response signature compared to classical endoplasmic reticulum (ER) stress, highlighting ER-associated degradation (ERAD) as a key adaptive pathway. While SW016789 reduces ERAD substrate OS-9 levels, broader ERAD component changes are limited in cell lines. However,"],"journal":["Cell reports"],"pubmed_title":["VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells."],"pmcid":["PMC12266945"],"funding_grant_id":["SCR_014387","U54 AG065181","R21 CA264339","RC2 DK125961","P30CA082709","UC4 DK098085","MDBR-24-19-CHI","T32 DK064466","IK2 BX004659","1R01GM148970","P30 DK097512","UL1 TR002529","7-21-PDF-157","R01 DK101573","2UC4DK098085","P30 CA082709","R01 GM148970","1R21CA264339","U54AG065181","UL1TR002529","R01 DK102948"],"pubmed_authors":["Rodrigues-Dos-Santos K","Attie AD","Johnson TS","Binns DD","Emfinger CH","Mosley AL","Ordonez A","Templin AT","Keller MP","Kuntz RL","Kwakye MB","Richardson TI","Roy G","Mukherjee N","Tan Z","Schueler KL","King GC","Doud EH","Kalwat MA"],"additional_accession":[]},"is_claimable":false,"name":"VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.","description":"β cells are dysfunctional in type 2 diabetes (T2D) and congenital hyperinsulinism (HI), but the mechanisms linking hypersecretion to β cell failure are poorly understood. Here, we use proteomics and functional assays in human and mouse β cell lines to identify VDAC1 as a target for the small molecule hypersecretion inducer SW016789. By enhancing membrane depolarization, SW016789 acutely increases Ca<sup>2+</sup> influx, eventually driving β cell dysfunction. Time-course transcriptomics analysis reveals a distinct hypersecretory response signature compared to classical endoplasmic reticulum (ER) stress, highlighting ER-associated degradation (ERAD) as a key adaptive pathway. While SW016789 reduces ERAD substrate OS-9 levels, broader ERAD component changes are limited in cell lines. However,","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-07-15T14:17:16.178Z","creation":"2025-08-12T03:04:59.763Z"},"accession":"S-EPMC12266945","cross_references":{"pubmed":["40512624"],"doi":["10.1016/j.celrep.2025.115834"]}}