{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:37:44Z","timestamp":1770485864720,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"General Research Fund"},{"name":"The Research Grants Council of Hong Kong Special Administrative Region, China","award":["CUHK 14107415"],"award-info":[{"award-number":["CUHK 14107415"]}]},{"name":"The Research Grants Council of Hong Kong Special Administrative Region, China","award":["14110314"],"award-info":[{"award-number":["14110314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To elucidate the role of Na\n                      <jats:sup>+<\/jats:sup>\n                      \/H\n                      <jats:sup>+<\/jats:sup>\n                      exchanger 3 (NHE3) in sodium\u2010glucose co\u2010transporter 1 (SGLT1)\u2010mediated small intestinal brush border membrane (BBM) glucose absorption and its functional implications in type 2 diabetes mellitus (T2DM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Human jejunal samples were obtained from patients undergoing gastrectomy.\n                      <jats:sup>14<\/jats:sup>\n                      C\u2010glucose absorption was measured by liquid scintillation counting. NHE3 expression was suppressed by siRNA\u2010mediated knockdown or augmented in Caco2 cells. Glucose and insulin tolerance in\n                      <jats:italic>db\/db<\/jats:italic>\n                      and\n                      <jats:italic>m+\/db<\/jats:italic>\n                      mice was assessed with oral and intraperitoneal glucose tolerance tests, and an intraperitoneal insulin tolerance test. Insulin resistance and \u03b2\u2010cell function were assessed using homeostatic model assessment of insulin resistance and \u03b2\u2010cell function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NHE3 expression was upregulated in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mouse jejunal BBM and high\u2010glucose\u2010treated Caco2 cells. NHE3 blockade impaired SGLT1\u2010mediated glucose absorption in human jejunum,\n                      <jats:italic>m+\/db<\/jats:italic>\n                      and\n                      <jats:italic>db\/db<\/jats:italic>\n                      mouse jejunums, and Caco2 cells, via serum\/glucocorticoid\u2010regulated kinase 1 (SGK1). NHE3 knockdown suppressed SGLT1\u2010mediated glucose uptake and reduced mRNA and protein levels of SGK1 and SGLT1, which were conversely enhanced by NHE3 overexpression. Chronic S3226 treatment diminished postprandial glucose levels and ameliorated glucose intolerance in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NHE3 is essential in the modulation of small intestinal BBM glucose absorption. Our findings provide a rationale for future possible clinical application of NHE3 for treatment of T2DM through reducing intestinal glucose uptake and counteracting postprandial hyperglycaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13151","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T04:26:36Z","timestamp":1510028796000},"page":"709-717","source":"Crossref","is-referenced-by-count":14,"title":["<scp>\n                      Na\n                      <sup>+<\/sup>\n                      \/H\n                      <sup>+<\/sup>\n                    <\/scp>\n                    exchanger 3 blockade ameliorates type 2 diabetes mellitus via inhibition of sodium\u2010glucose co\u2010transporter 1\u2010mediated glucose absorption in the small intestine"],"prefix":"10.1111","volume":"20","author":[{"given":"Leo K. Y.","family":"Chan","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enders K. W.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Surgery, Prince of Wales Hospital, Faculty of Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-3178","authenticated-orcid":false,"given":"Po Sing","family":"Leung","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"World Health Organization. Global report on diabetes 2016."},{"key":"e_1_2_6_3_1","volume-title":"Diabetes Atlas","author":"International Diabetes Federation","year":"2017"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.10.2405"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2745"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.014"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.07.005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.053"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00373.2015"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000276554"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00310.2001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00017.2012"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007790"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.201590"},{"issue":"7","key":"e_1_2_6_15_1","first-page":"91","article-title":"Role of intestinal Na+\/ H+ exchanger inhibition in the prevention of cardiovascular and kidney disease","volume":"3","author":"Yan J","year":"2015","journal-title":"Ann Transl Med"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7095352"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00562.2011"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00492.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374985"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79552"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1029"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354486"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.10.042"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602898200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.5.C1533"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.4.F565"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.10.017"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.2.262"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807502200"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2004.104"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2391"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.10.040"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03682.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.20.354"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11674-3"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479197"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1612"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13151","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:40:43Z","timestamp":1761889243000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,5]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/dom.13151"],"URL":"https:\/\/doi.org\/10.1111\/dom.13151","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,5]]}}}