{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:08:54Z","timestamp":1768450134667,"version":"3.49.0"},"reference-count":39,"publisher":"Korean Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004470","name":"Daewoong Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1C1-C2003297"],"award-info":[{"award-number":["2022R1C1-C2003297"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["042022-4080"],"award-info":[{"award-number":["042022-4080"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:p>Background: The prevalence of type 2 diabetes mellitus (T2DM) increases with age, and cellular senescence of pancreatic \u03b2-cells plays a key role in T2DM pathogenesis. As canagliflozin and acarbose have been shown to increase lifespan in mice, we investigated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, \u03b1-glucosidase inhibitor or both on the cellular senescence of \u03b2-cells in a T2DM mouse model.Methods: Enavogliflozin (0.3 mg\/kg), acarbose (10 mg\/kg), or vehicle was orally administered daily to &lt;i&gt;db\/db&lt;\/i&gt; mice for 6 weeks. The levels of senescence markers (&lt;i&gt;p16, p21,&lt;\/i&gt; and &lt;i&gt;p53&lt;\/i&gt;) in the pancreas and kidney were measured through real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot. In an &lt;i&gt;in vitro&lt;\/i&gt; analysis, isolated pancreatic islets were exposed to H&lt;sub&gt;2&lt;\/sub&gt;O&lt;sub&gt;2&lt;\/sub&gt; to induce cellular senescence, then treated with \u03b2-hydroxybutyrate (\u03b2-HB), and subsequently assessed for levels of senescent markers.Results: Enavogliflozin alone or combined with acarbose effectively lowered blood glucose levels in &lt;i&gt;db\/db&lt;\/i&gt; mice. The combined treatment resulted in the greatest increase in \u03b2-cell function calculated using insulinogenic index and homeostasis model assessment of \u03b2-cell function compared to the vehicle. Additionally, the combined treatment significantly reversed the increase in &lt;i&gt;p16,&lt;\/i&gt; with a similar trend observed in &lt;i&gt;p21&lt;\/i&gt; and &lt;i&gt;p53&lt;\/i&gt; in the islets. Treatment increased circulating \u03b2-HB and &lt;i&gt;in vitro&lt;\/i&gt; analysis suggested the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by \u03b2-HB in reducing senescence in the islets.Conclusion: The combined administration of enavogliflozin and acarbose significantly reduced blood glucose, improved \u03b2-cell function, and reduced senescent \u03b2-cells in &lt;i&gt;db\/db&lt;\/i&gt; mice. This combination therapy holds potential as a senotherapeutic strategy for managing T2DM.<\/jats:p>","DOI":"10.4093\/dmj.2024.0339","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:03:21Z","timestamp":1747875801000},"page":"1229-1241","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and \u03b1-Glucosidase in a Type 2 Diabetes Mellitus Animal Model"],"prefix":"10.4093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7109-7084","authenticated-orcid":true,"given":"Serin","family":"Hong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-7422","authenticated-orcid":true,"given":"Byung Soo","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-5868","authenticated-orcid":true,"given":"Hyunsuk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-6126","authenticated-orcid":true,"given":"Young Min","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(09)60619-x"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(15)00336-8"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1172\/jci7231"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00037"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.006"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.015"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.021"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nature05092"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1172\/jci200422475"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4054"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133668"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000599"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0553"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00865.x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2022.0416"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3823"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01923-y"},{"key":"ref19","first-page":"e12950","volume-title":"Targeting senescent cells alleviates obesity-induced metabolic dysfunction","author":"Palmer","year":"2019"},{"key":"ref20","first-page":"184","volume-title":"Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan","author":"Baker","year":"2016"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6659"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140019"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00642-y"},{"key":"ref24","first-page":"2561","volume-title":"Sodium-glucose cotransporter-2 inhibition reduces cellular senescence in the diabetic kidney by promoting ketone body-induced NRF2 activation","author":"Kim","year":"2021"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12898"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.137474"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-019-1494-7"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2022.0117"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.150"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12699"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12387"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01832"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204896"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123130"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22065"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00132.2020"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048.896"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.2337\/dcs15-3007"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.3803\/enm.2023.1816"}],"container-title":["Diabetes &amp; 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