{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:16Z","timestamp":1792384876700,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018617","name":"Liaoning Revitalization Talents Program","doi-asserted-by":"publisher","award":["XLYC2412003"],"award-info":[{"award-number":["XLYC2412003"]}],"id":[{"id":"10.13039\/501100018617","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) is a major cause of renal failure and end\u2010stage renal disease. Pyroptosis, a Gasdermin\u2010dependent inflammatory form of programmed cell death, has been implicated in DKD progression. Metformin has shown renoprotective effects in DKD; however, the underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether metformin attenuates high glucose\u2010induced pyroptosis and inflammatory responses in HK\u20102 cells through SIRT1\u2010mediated regulation of the TXNIP\/NLRP3 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bioinformatics analyses were performed to identify DKD\u2010related pyroptosis\u2010associated genes and enriched pathways. Serum TXNIP and IL\u20101\u03b2 levels were measured in patients with type 2 diabetes mellitus stratified by urinary albumin\u2010to\u2010creatinine ratio (UACR). HK\u20102 cells were exposed to high glucose (30\u2009mM) to establish an in\u00a0vitro injury model. Oxidative stress, pyroptosis\u2010related signalling and inflammatory cytokines were evaluated using molecular and immunological assays. SIRT1 modulation and TXNIP silencing were used to investigate pathway regulation. Chromatin immunoprecipitation assays were performed to assess SIRT1 occupancy and histone acetylation status within the TXNIP promoter region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pyroptosis\u2010related genes were mainly enriched in inflammatory and NLRP3 inflammasome\u2010associated pathways. Serum TXNIP and IL\u20101\u03b2 levels were elevated in DKD patients and positively correlated with UACR. In HK\u20102 cells, high glucose reduced SIRT1 expression and activated the TXNIP\/NLRP3 inflammasome pathway, accompanied by increased GSDMD cleavage and inflammatory cytokine expression. Metformin partially reversed these changes. Altered SIRT1 activity was also associated with changes in H3K56 acetylation enrichment within the TXNIP promoter region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metformin may alleviate high glucose\u2010induced pyroptosis and inflammatory responses in HK\u20102 cells, potentially through modulation of SIRT1\u2010associated TXNIP\/NLRP3 signalling and TXNIP\u2010related chromatin acetylation status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71248","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:33:19Z","timestamp":1787193199000},"page":"10343-10369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Alleviates High Glucose\u2010Induced Pyroptosis and Inflammatory Responses in\n                    <scp>HK<\/scp>\n                    \u20102 Cells via\n                    <scp>SIRT1<\/scp>\n                    \u2010Associated Regulation of the\n                    <scp>TXNIP<\/scp>\n                    \/\n                    <scp>NLRP3<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"28","author":[{"given":"Shuyu","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The First Affiliated Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of China Medical University  Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The First Affiliated Hospital of China Medical University  Shenyang Liaoning 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