{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:46:20Z","timestamp":1789231580689,"version":"build-2803163510"},"reference-count":40,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":70,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To assess the effects of empagliflozin, a selective sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor, on broad biological systems through proteomics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Aptamer-based proteomics was used to quantify 3,713 proteins in 144 paired plasma samples obtained from 72 participants across the spectrum of glucose tolerance before and after 4 weeks of empagliflozin 25 mg\/day. The biology of the plasma proteins significantly changed by empagliflozin (at false discovery rate\u2013corrected P &amp;lt; 0.05) was discerned through Ingenuity Pathway Analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Empagliflozin significantly affected levels of 43 proteins, 6 related to cardiomyocyte function (fatty acid\u2013binding protein 3 and 4 [FABPA], neurotrophic receptor tyrosine kinase, renin, thrombospondin 4, and leptin receptor), 5 to iron handling (ferritin heavy chain 1, transferrin receptor protein 1, neogenin, growth differentiation factor 2 [GDF2], and \u03b22-microglobulin), and 1 to sphingosine\/ceramide metabolism (neutral ceramidase), a known pathway of cardiovascular disease. Among the protein changes achieving the strongest statistical significance, insulin-like binding factor protein-1 (IGFBP-1), transgelin-2, FABPA, GDF15, and sulphydryl oxidase 2 precursor were increased, while ferritin, thrombospondin 3, and Rearranged during Transfection (RET) were decreased by empagliflozin administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>SGLT2 inhibition is associated, directly or indirectly, with multiple biological effects, including changes in markers of cardiomyocyte contraction\/relaxation, iron handling, and other metabolic and renal targets. The most significant differences were detected in protein species (GDF15, ferritin, IGFBP-1, and FABP) potentially related to the clinical and metabolic changes that were actually measured in the same patients. These novel results may inform further studies using targeted proteomics and a prospective design.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc20-0456","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T22:05:12Z","timestamp":1591913112000},"page":"2183-2189","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":59,"title":["Mechanisms of Sodium\u2013Glucose Cotransporter 2 Inhibition: Insights From Large-Scale Proteomics"],"prefix":"10.2337","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-1584","authenticated-orcid":false,"given":"Ele","family":"Ferrannini","sequence":"first","affiliation":[{"name":"CNR Institute of Clinical Physiology, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin C.","family":"Murthy","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Hospital of the 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