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Rapatar is a novel nanoformulated micellar of rapamycin, a putative inhibitor of mTOR that has been rationally designed to increase water solubility of rapamycin to facilitate p.o. administration and enhance bioavailability. We examined the effect of Rapatar on the metabolic status and protection against myocardial I\/R injury in type 2 diabetic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Adult male db\/db mice were treated daily for 10\u00a0weeks with Rapatar (0.75\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, p.o.) or vehicle. Isolated hearts were connected to a Langendorff perfusion system and subjected to global ischaemia (30\u00a0min) and reperfusion (1\u00a0h).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Rapatar reduced fasting plasma glucose and triglyceride levels, prevented the gain in body weight and also improved glucose tolerance and insulin sensitivity in db\/db mice compared with control. Cardiac function was improved following Rapatar treatment in db\/db mice. Myocardial infarct size was reduced in Rapatar\u2010treated mice with improved post\u2010ischaemic rate\u2013force product. Western blot analyses demonstrated a significant inhibition of phosphorylation of ribosomal protein <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.guidetopharmacology.org\/GRAC\/ObjectDisplayForward?objectId=1525\">S6<\/jats:ext-link> (downstream target of mTORC1), but not Akt (Ser<jats:sup>473<\/jats:sup>, target of mTORC2) following chronic treatment with Rapatar. Rapatar also induced phosphorylation of AMPK, STAT3, ERK1\/2 and glycogen synthase kinase 3\u03b2, without interfering with phosphorylation of p38.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications<\/jats:title><jats:p>Our studies indicate that chronic treatment with Rapatar improves metabolic status and cardiac function with a reduction of infarct size following myocardial I\/R injury in diabetic mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14059","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T01:02:36Z","timestamp":1506906156000},"page":"4771-4784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Chronic treatment with novel nanoformulated micelles of rapamycin, Rapatar, protects diabetic heart against ischaemia\/reperfusion injury"],"prefix":"10.1111","volume":"174","author":[{"given":"Arun","family":"Samidurai","sequence":"first","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology Virginia Commonwealth University  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi N","family":"Salloum","sequence":"additional","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology Virginia Commonwealth University  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Durrant","sequence":"additional","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology Virginia Commonwealth University  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga B","family":"Chernova","sequence":"additional","affiliation":[{"name":"Everon Biosciences, Inc.  Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh C","family":"Kukreja","sequence":"additional","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology Virginia Commonwealth University  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-7277","authenticated-orcid":false,"given":"Anindita","family":"Das","sequence":"additional","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology Virginia Commonwealth University  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13347"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703829"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.506"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.08.031"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096075"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100496"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.521062"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.10.003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.09.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0486-5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00100.2009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404706200"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801547200"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0878"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4619720"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0728-x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(91)90218-L"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00692.2008"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.160614"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1324"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0921"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.04.014"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1215135"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.178"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3929"},{"key":"e_1_2_10_31_1","first-page":"791","article-title":"Xylobiose, an alternative sweetener, ameliorates diabetes\u2010related metabolic changes by regulating hepatic lipogenesis and miR\u2010122a\/33a in db\/db mice","volume":"8","author":"Lim E","year":"2016","journal-title":"Forum Nutr"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65268"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00707.2010"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509225"},{"key":"e_1_2_10_36_1","unstructured":"PietrzynskiG AlakhovV PatelK(2016).Rapamycin composition. 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