{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:40:34Z","timestamp":1790404834530,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102016R1A5A1010764"],"award-info":[{"award-number":["NRF\u20102016R1A5A1010764"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004083","name":"MSIP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","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":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate sodium\u2010glucose cotransporter 2 inhibitor (SGLT2i)\u2010induced changes in ketogenic enzymes and transporters in normal and diabetic mice models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Normal mice were randomly assigned to receive either vehicle or SGLT2i (25\u2009mg\/kg\/d by oral gavage) for 7\u2009days. Diabetic mice were treated with vehicle, insulin (4.5\u2009units\/kg\/d by subcutaneous injection) or SGLT2i (25\u2009mg\/kg\/d by intra\u2010peritoneal injection) for 5\u2009weeks. Serum and tissues of ketogenic organs were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both normal and diabetic mice, SGLT2i increased beta\u2010hydroxybutyrate (BHB) content in liver, kidney and colon tissue, as well as in serum and urine. In these organs, SGLT2i upregulated mRNA expression of ketogenic enzymes, 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A synthase 2 and 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A lyase. Similar patterns were observed in the kidney, ileum and colon for mRNA and protein expression of sodium\u2010dependent monocarboxylate transporters (SMCTs), which mediate the cellular uptake of BHB and butyrate, an important substrate for intestinal ketogenesis. In diabetic mice under euglycaemic conditions, SGLT2i increased major ketogenic enzymes and SMCTs, while insulin suppressed ketogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SGLT2i increased systemic and tissue BHB levels by upregulating ketogenic enzymes and transporters in the liver, kidney and intestine, suggesting the integrated physiological consequences for ketone body metabolism of SGLT2i administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13577","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T10:06:47Z","timestamp":1541671607000},"page":"801-811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Sodium\u2010glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter\u2010organ crosstalk"],"prefix":"10.1111","volume":"21","author":[{"given":"Jin Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Brain Korea 21 PLUS Project for Medical Science Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9333-7512","authenticated-orcid":false,"given":"Minyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Ra","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine National Health Insurance Service Ilsan Hospital  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-4992","authenticated-orcid":false,"given":"Byung\u2010Wan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Endocrine Research, Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0364-4675","authenticated-orcid":false,"given":"Eun Seok","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Endocrine Research, Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0542-2854","authenticated-orcid":false,"given":"Bong\u2010Soo","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Endocrine Research, Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Won","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Glycosylation Network Research Center, Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-4942","authenticated-orcid":false,"given":"Yong\u2010ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Brain Korea 21 PLUS Project for Medical Science Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Internal Medicine Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Graduate School Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Endocrine Research, Yonsei University College of Medicine  Seoul Korea"},{"name":"Department of Systems Biology Glycosylation Network Research Center, Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.170"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2014.38.4.261"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40119-016-0069-z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1596"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-5996-7-S1-A58"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw110"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2016.31.2.239"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2724"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1356"},{"key":"e_1_2_7_13_1","first-page":"33","article-title":"Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: basic mechanisms and therapeutic perspectives","author":"Qiu H","year":"2017","journal-title":"Diabetes Metab Res Rev"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3196-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3845-8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2017.09.006"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1884"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-595X(83)80046-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.022"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2016.04.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.06.005"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0090342"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1363"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00308.2010"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(96)80193-0"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074869"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112118"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1030514"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1120595"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050927"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-008-9022-y"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.10.028"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1300785"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017355"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0542"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.08.005"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227166"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3804"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.004"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25102"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.05.001"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20011699"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01648-3"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122093"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.0590051695.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007121313"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-016-0122-x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0940015C"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00033.2010"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00087.2014"},{"key":"e_1_2_7_51_1","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.1016\/S0021-9258(19)84548-9","article-title":"Site\u2010site interaction in the phospholipid activation of D\u2010beta\u2010hydroxybutyrate dehydrogenase","volume":"261","author":"Sandermann H","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(88)90428-6"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(75)90004-9"},{"key":"e_1_2_7_54_1","first-page":"F762","article-title":"Transport of beta\u2010hydroxybutyrate and acetoacetate along rat nephrons: a micropuncture study","volume":"262","author":"Ferrier B","year":"1992","journal-title":"Am J Physiol"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163795"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-016-0069-y"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.36.279"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbj.2016.04.004"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00279.2010"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00104.2015"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.13"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3828"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34462-X"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12881"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610050304"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1167"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.348"},{"key":"e_1_2_7_68_1","first-page":"E253","article-title":"Validation of a tracer technique to determine nonsteady\u2010state ketone body turnover rates in man","volume":"240","author":"Keller U","year":"1981","journal-title":"Am J Physiol"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2040399"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.13577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.13577","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:40:43Z","timestamp":1761867643000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,4]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/dom.13577"],"URL":"https:\/\/doi.org\/10.1111\/dom.13577","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,4]]},"assertion":[{"value":"2018-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}