{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:41:17Z","timestamp":1790109677950,"version":"4.0.1"},"reference-count":30,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA028506"],"award-info":[{"award-number":["R01AA028506"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK097512"],"award-info":[{"award-number":["P30DK097512"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK120689"],"award-info":[{"award-number":["R01DK120689"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK121925"],"award-info":[{"award-number":["R01DK121925"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK124612"],"award-info":[{"award-number":["R01DK124612"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21AG072288"],"award-info":[{"award-number":["R21AG072288"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricks Family Foundation"},{"DOI":"10.13039\/100001377","name":"Walther Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA082709"],"award-info":[{"award-number":["P30CA082709"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Pancreatic \u03b2-cells undergo senescence and loss during aging; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate what sirtuin 6 (SIRT6) does during \u03b2-cell aging. Pancreatic \u03b2-cell\u2013specific Sirt6 transgenic (TgSIRT6) mice were generated for this study. DNA damage, cell death, and cell proliferation were analyzed in cell and mouse models. SIRT6 protein levels were decreased in pancreatic \u03b2-cells during aging. TgSIRT6 mice exhibited less DNA damage and cell death, including apoptosis, necroptosis, and pyroptosis, in \u03b2-cells than control mice. TgSIRT6 mice had increased total islet area and mass in pancreas compared with control mice. As a result, TgSIRT6 mice showed better glucose tolerance and glucose-stimulated insulin secretion than control mice. RRAD and GEM-like GTPase 2 (REM2), an endogenouse inhibitor of high-voltage\u2013activated calcium channels, was negatively regulated by SIRT6. Knockdown of Rem2 in INS-1 cells partially rescued the SIRT6 deficiency\u2013 and palmitic acid\u2013induced DNA damage, lipid peroxidation, and cell death. Rem2 \u03b2-cell\u2013specific knockout mice had less DNA damage and cell death in \u03b2-cells than control mice. Our data suggest that SIRT6 is a critical antiaging factor in pancreatic \u03b2-cells and is a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Pancreatic \u03b2-cell function declines with age, but the underlying mechanism is poorly understood. In this study, we attempted to address how to reverse \u03b2-cell aging. Our data showed that sirtuin 6 (SIRT6) overexpression can reduce age-associated DNA damage, cell death, and functional decline in \u03b2-cells. Our findings suggest that improving Sirt6 gene expression and function may slow down \u03b2-cell decline in older patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0116","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T15:34:57Z","timestamp":1755790497000},"page":"1976-1991","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":6,"title":["SIRT6 Is a Key Regulator of Pancreatic \u03b2-Cell Survival and Function During Aging"],"prefix":"10.2337","volume":"74","author":[{"given":"Jimin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandali D.","family":"Lokuge","sequence":"additional","affiliation":[{"name":"Luddy School of Informatics, Computing, and Engineering, Indiana University 2 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"},{"name":"Center for Diabetes and Metabolic Diseases, School of Medicine, Indiana University 3 , Indianapolis, IN"},{"name":"Melvin & Bren Simon Comprehensive Cancer Center, School of Medicine, Indiana University 4 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Melvin & Bren Simon Comprehensive Cancer Center, School of Medicine, Indiana University 4 , Indianapolis, IN"},{"name":"Department of Medical and Molecular Genetics, School of Medicine, Indiana University 5 , Indianapolis, IN"},{"name":"Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University 6 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar","family":"Katturajan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinn","family":"Marakovits","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Indiana University 7 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wan","sequence":"additional","affiliation":[{"name":"Luddy School of Informatics, Computing, and Engineering, Indiana University 2 , Indianapolis, IN"},{"name":"Melvin & Bren Simon Comprehensive Cancer Center, School of Medicine, Indiana University 4 , Indianapolis, IN"},{"name":"Department of Medical and Molecular Genetics, School of Medicine, Indiana University 5 , Indianapolis, IN"},{"name":"Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University 6 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5452-6882","authenticated-orcid":false,"given":"X. Charlie","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Indiana University 1 , Indianapolis, IN"},{"name":"Luddy School of Informatics, Computing, and Engineering, Indiana University 2 , Indianapolis, IN"},{"name":"Center for Diabetes and Metabolic Diseases, School of Medicine, Indiana University 3 , Indianapolis, IN"},{"name":"Department of Medical and Molecular Genetics, School of Medicine, Indiana University 5 , Indianapolis, IN"},{"name":"Center for Computational Biology and Bioinformatics, School of Medicine, Indiana University 6 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"2026061115081775000_B1","doi-asserted-by":"crossref","first-page":"101674","DOI":"10.1016\/j.arr.2022.101674","article-title":"The pancreatic \u03b2-cell in ageing: implications in age-related 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