{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:29:43Z","timestamp":1770748183386,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2016,10,31]],"date-time":"2016-10-31T00:00:00Z","timestamp":1477872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project of National Great New Drug Research and Development","award":["2012ZX09503001-001"],"award-info":[{"award-number":["2012ZX09503001-001"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ15H280008"],"award-info":[{"award-number":["LQ15H280008"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ16H280002"],"award-info":[{"award-number":["LQ16H280002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography\/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC\/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments.<\/jats:p>","DOI":"10.3390\/molecules21111446","type":"journal-article","created":{"date-parts":[[2016,10,31]],"date-time":"2016-10-31T11:09:46Z","timestamp":1477912186000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Urinary Metabolomic Profiling in Zucker Diabetic Fatty Rats with Type 2 Diabetes Mellitus Treated with Glimepiride, Metformin, and Their Combination"],"prefix":"10.3390","volume":"21","author":[{"given":"Yu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, No. 132, Tianmushan Road, Hangzhou 310007, China"},{"name":"College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Shou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, No. 132, Tianmushan Road, Hangzhou 310007, China"},{"name":"Department of Chemistry, Xixi Campus, Zhejiang University, No. 148, Tianmushan Road, Hangzhou 310028, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Yu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.diabres.2013.11.002","article-title":"Global estimates of diabetes prevalence for 2013 and projections for 2035","volume":"3","author":"Guariguata","year":"2014","journal-title":"Diabetes Res. 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