{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:14:35Z","timestamp":1788491675523,"version":"build-2803163510"},"reference-count":50,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"NIH\/NIGMS","award":["T32GM008111"],"award-info":[{"award-number":["T32GM008111"]}]},{"name":"NIH\/National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK111483"],"award-info":[{"award-number":["DK111483"]}]},{"name":"NIH\/National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK126456"],"award-info":[{"award-number":["DK126456"]}]},{"name":"NIH\/National Institute of Diabetes and Digestive and Kidney Diseases","award":["DK128132"],"award-info":[{"award-number":["DK128132"]}]},{"name":"NIH\/National Institute of Diabetes and Digestive and Kidney Diseases","award":["F31 DK137440"],"award-info":[{"award-number":["F31 DK137440"]}]},{"name":"NIH\/National Institute of Diabetes and Digestive and Kidney Diseases","award":["F31DK111181"],"award-info":[{"award-number":["F31DK111181"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetes is characterized by a loss of functional \u03b2-cell mass; therefore, identifying factors involved in establishing and preserving \u03b2-cells is critical to combat rising diabetes incidence. While transcription factors are crucial \u03b2-cell regulators, knowledge of coregulators facilitating gene expression is limited. Previously, we demonstrated that the islet-1 (Isl1) transcription factor forms complexes with ubiquitin ligases ring finger 20 (Rnf20) and Rnf40 to regulate \u03b2-cells in\u00a0vitro. Here, we investigated whether Rnf20-mediated complexes are required for \u03b2-cell function in adult islets by characterizing a novel \u03b2-cell\u2013enriched Rnf20 knockout mouse model. Tamoxifen induction of Rnf20 recombination prompted a robust loss of histone 2B monoubiquitination, imparted severe hyperglycemia and glucose intolerance, and elicited an overall reduction in insulin content. Expression of mRNAs and proteins involved in glucose-stimulated insulin secretion and \u03b2-cell identity were also dysregulated in Rnf20\u0394\u03b2-cell mice. Comparative analyses of the loss of either Rnf20 or Isl1 yielded similar changes in the \u03b2-cell regulome, supporting that Isl1::Rnf20 complexes are critical regulators of \u03b2-cell identity and function. Isl1::Rnf20 complexes are maintained in human tissues wherein they regulate insulin expression, secretion, and content. These findings increase our understanding of key players in \u03b2-cell maintenance, which is crucial for the advancement of \u03b2-cell derivation diabetes therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Transcription factor Islet-1 (Isl1) and ubiquitin ligase Ring Finger 20 (Rnf20) complexes regulate insulin secretion and \u03b2-cell gene expression in\u00a0vitro. Loss of Rnf20 in adult \u03b2-cells disrupts \u03b2-cell identity and insulin processing, production, and secretion. In complex with Isl1, Rnf20 influences the \u03b2-cell regulome and supports proper glucose homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0167","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T21:51:41Z","timestamp":1753998701000},"page":"1814-1824","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["The Islet-1 Interaction Partner Rnf20 Regulates Glucose Homeostasis and Pancreatic \u03b2-Cell Identity"],"prefix":"10.2337","volume":"74","author":[{"given":"Tanya H.","family":"Pierre","sequence":"first","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maigen M.","family":"Bethea","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Liu","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University 2 , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University 2 , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil","family":"Chada","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, Department of Medicine, University of California at San Diego 3 , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University 4 , Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushant","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland W.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University 2 , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-447X","authenticated-orcid":false,"given":"Chad S.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"2026061114472286400_B1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fgene.2017.00035","article-title":"Evidence for loss in identity, de-differentiation, and trans-differentiation of islet \u03b2-cells in type 2 diabetes","volume":"8","author":"Hunter","year":"2017","journal-title":"Front Genet"},{"key":"2026061114472286400_B2","doi-asserted-by":"crossref","first-page":"756548","DOI":"10.3389\/fimmu.2021.756548","article-title":"Partners in crime: beta-cells and autoimmune responses complicit in type 1 diabetes pathogenesis","volume":"12","author":"Toren","year":"2021","journal-title":"Front Immunol"},{"key":"2026061114472286400_B3","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.tem.2021.04.011","article-title":"Transcriptional mechanisms of pancreatic \u03b2-cell maturation and functional 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