{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:53:39Z","timestamp":1790178819763,"version":"4.1.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01DK240923"],"award-info":[{"award-number":["5R01DK240923"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\u03b2-Cell dysfunction is a core defect in T2DM, and chronic, sustained hyperglycemia has been implicated in progressive \u03b2-cell failure, ie, glucotoxicity. The aim of the present study was to examine the effect of lowering the plasma glucose concentration with dapagliflozin, a glucosuric agent, on \u03b2-cell function in T2DM individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research Design and Methods:<\/jats:title>\n                    <jats:p>Twenty-four subjects with T2DM received dapagliflozin (n = 16) or placebo (n = 8) for 2 weeks, and a 75-g oral glucose tolerance test (OGTT) and insulin clamp were performed before and after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured during the OGTT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Dapagliflozin significantly lowered both the fasting and 2-hour plasma glucose concentrations and the incremental area under the plasma glucose concentration curve (\u0394G0\u2013120) during OGTT by \u221233 \u00b1 5 mg\/dL, \u221273 \u00b1 9 mg\/dL, and \u221260 \u00b1 12 mg\/dL \u00b7 min, respectively, compared to \u221213 \u00b1 9, \u221233 \u00b1 13, and \u221218 \u00b1 9 reductions in placebo-treated subjects (both P &amp;lt; .01). The incremental area under the plasma C-peptide concentration curve tended to increase in dapagliflozin-treated subjects, whereas it did not change in placebo-treated subjects. Thus, \u0394C-Pep0\u2013120\/\u0394G0\u2013120 increased significantly in dapagliflozin-treated subjects, whereas it did not change in placebo-treated subjects (0.019 \u00b1 0.005 vs 0.002 \u00b1 0.006; P &amp;lt; .01). Dapagliflozin significantly improved whole-body insulin sensitivity (insulin clamp). Thus, \u03b2-cell function, measured as \u0394C-Pep0\u2013120\/ \u0394G0\u2013120 \u00f7 insulin resistance, increased by 2-fold (P &amp;lt; .01) in dapagliflozin-treated vs placebo-treated subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Lowering the plasma glucose concentration with dapagliflozin markedly improves \u03b2-cell function, providing strong support in man for the glucotoxic effect of hyperglycemia on \u03b2-cell function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2014-3472","type":"journal-article","created":{"date-parts":[[2015,2,24]],"date-time":"2015-02-24T13:11:52Z","timestamp":1424783512000},"page":"1927-1932","source":"Crossref","is-referenced-by-count":163,"title":["Dapagliflozin Lowers Plasma Glucose Concentration and Improves \u03b2-Cell Function"],"prefix":"10.1210","volume":"100","author":[{"given":"Aurora","family":"Merovci","sequence":"first","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mari","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche Institute of Biomedical Engineering (A.Ma.), 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Solis","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Daniele","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Chavez-Velazquez","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devjit","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scheherezada","family":"Urban McCarthy","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Abdul-Ghani","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A.","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"Division of Diabetes (A.Me., C.S., G.D., A.C.-V., D.T., S.U.M., M.A.-G., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616360085900_B1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. 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