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Since there is accumulating evidence that AGEs and their receptor (RAGE) play a crucial role in diabetes-related complications, we examined here whether empagliflozin ameliorates renal and metabolic derangements in db\/db mice, an obese type 2 diabetes animal by blocking the AGE-RAGE axis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Eight-week-old db\/db mice were fed a 0.045% empagliflozin diet (db\/db\u2009+\u2009Empa) or normal diet (db\/db) for 13\u00a0weeks. The same week-old db\/\u2009+\u2009m mice were maintained on normal diet (db\/\u2009+\u2009m) used as a control. At baseline and 13\u00a0weeks after intervention, biochemical analyses in the serum and urine were performed, and kidneys and adipose tissues were obtained for morphological, immunohistochemical, and reverse transcription-polymerase chain reaction analyses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Empagliflozin treatment for 13\u00a0weeks significantly reduced AGEs, <jats:italic>N<\/jats:italic>\n              <jats:sup>\u03b5<\/jats:sup>-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), RAGE, NADPH oxidase-derived oxidative stress, inflammatory and fibrotic reactions in the kidneys of db\/db mice of 21-week-old in association with attenuation of glomerular extracellular matrix accumulation, podocyte loss, proteinuria, and tubulointerstitial damage. Empagliflozin also reduced the AGE-RAGE-oxidative stress-induced inflammatory reactions in the adipose tissues of db\/db mice, which was associated with restoration of adiponectin levels and decreased insulin resistance. Serum MG-H1 levels of control and db\/db mice at 21\u00a0weeks of age were significantly associated with proteinuria, tubulointerstitial damage, tissue AGEs levels, and serum monocyte chemoattractant protein-1 and adiponectin (inversely) values.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our present findings suggest that empagliflozin could ameliorate renal and metabolic derangements in type 2 diabetes animals by attenuating the AGE-RAGE axis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s10020-025-01138-0","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T20:05:16Z","timestamp":1741291516000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Empagliflozin ameliorates renal and metabolic derangements in obese type 2 diabetic mice by blocking advanced glycation end product\u2013receptor axis"],"prefix":"10.1186","volume":"31","author":[{"given":"Takanori","family":"Matsui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Sotokawauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Koga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho-ichi","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"issue":"3","key":"1138_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2022.102441","volume":"16","author":"KA Adeshara","year":"2022","unstructured":"Adeshara KA, Bangar N, Diwan AG, Tupe RS. 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