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Since the anti\u2010inflammatory agent nimesulide selectively inhibited B0AT1 in vitro, we hypothesized that nimesulide exhibits in vivo potential to restrict neutral amino acid absorption and, therefore, may improve insulin sensitivity. The dose\u2010related effect of nimesulide (10 to 100\u2009mg\/kg, PO) on intestinal absorption of neutral amino acids was estimated in C57 mice. The effect of nimesulide (50\u2009mg\/kg, PO) on renal resorption of amino acids was also assessed. The effect of chronic nimesulide (50\u2009mg\/kg, PO, BID for 14\u2009days) was assessed in high protein diet\u2010fed C57 mice, diet\u2010induced obese mice and obese and diabetic db\/db mice. Acute and chronic nimesulide treatment decreased absorption of neutral amino acids and increased their urinary excretion. Nimesulide treatment improved insulin sensitivity and glycemic control, increased GLP\u20101, decreased liver lipids and improved FGF\u201021 in serum. Nimesulide improved insulin sensitivity and glucose tolerance by inhibiting neutral amino acid transport in the intestine and kidneys. Thus, it can serve as a tool compound for in vivo B0AT1 inhibition.<\/jats:p>","DOI":"10.1111\/bcpt.13670","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T18:08:05Z","timestamp":1633975685000},"page":"35-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In vivo antidiabetic activity of nimesulide due to inhibition of amino acid transport"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-4371","authenticated-orcid":false,"given":"Amit","family":"Joharapurkar","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samadhan","family":"Kshirsagar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maulik","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardikkumar","family":"Savsani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukul","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Cadila Healthcare Limited  Ahmedabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.25.050304.092545"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-013-0255-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.02.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.03.014"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13492"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90173-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.1994.32.7.525"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.10.2112"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2006.09.008"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-020-02930-4"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.022"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2013-0189"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2014-0310"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.39740"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00140"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16568-z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2627"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.4182"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-015-1075-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200225090-00003"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357001774255"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2674"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12938"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2019.03.010"}],"container-title":["Basic &amp; 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