{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:06:47Z","timestamp":1789204007213,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":254,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010apoptosis is a critical pathological event in diabetes mellitus (DM), yet effective therapeutic agents that directly protect\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cells are lacking. Polydatin (PD), a natural stilbenoid, has shown potential in regulating glucolipid metabolism; however, its role and mechanism in protecting pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cells from apoptosis remain largely unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The present work focused on investigating whether PD prevents pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cells against diabetes\u2010related apoptosis and exploring the associated molecular mechanisms, with a particular focus on the TNF\/TNF\u2010R1\/caspase\u20103 signaling axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Network pharmacology and bioinformatics were applied in combination with experimental validation. Potential targets of PD and DM were retrieved from public databases. Key candidate targets were screened via protein\u2013protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) regression, functional enrichment (GO\/KEGG), differential expression, receiver operating characteristic (ROC), and clinical correlation analyses. Binding interactions were assessed by molecular docking alongside dynamic simulations. In vitro and in vivo DM models were established with high glucose (HG)\u2013stimulated MIN6\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cells and high\u2010fat\/HG diet\u2010fed mice with low\u2010dose streptozotocin (STZ) administration, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TNF was identified as a central target of PD against DM, with elevated expression under diabetic conditions and a significant correlation with fasting blood glucose levels. PD exhibited strong binding affinity to both TNF (Vina score: \u20138.9\u2009kcal\u00b7mol\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) and TNF\u2010R1 (Vina score: \u20138.8\u2009kcal\u00b7mol\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Cellular experiments demonstrated that PD enhanced\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell cycle progression (upregulated Ki67 expression), downregulated TNF\u2010R1 expression, and facilitated insulin secretion under HG stimulation. In diabetic mice, PD significantly increased the islet\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell mass and area; downregulated the expression of TNF, TNF\u2010R1, and cleaved\u2010caspase\u20103; and restored PARP1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study revealed that PD attenuated diabetic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010apoptosis, likely through inhibition of the TNF\/TNF\u2010R1\/caspase\u20103 pathway, suggesting that PD may be a novel anti\u2010DM therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/9073132","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:44:33Z","timestamp":1789202673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polydatin Reverses Diabetes\u2010Induced Apoptosis of Pancreatic\n                    <i>\u03b2<\/i>\n                    \u2010Cells by Inhibiting the TNF\/TNF\u2010R1\/Caspase\u20103 Signaling 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