{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:42:18Z","timestamp":1780584138382,"version":"3.54.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T00:00:00Z","timestamp":1481241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,3]]},"abstract":"\n Aims<\/jats:title>\n To compare the therapeutic potential of TP\u2010113, a unique molecular entity linking DHA with metformin, for alleviating insulin resistance in obese diabetic mice through the PDX\/IL\u20106 pathway.<\/jats:p>\n <\/jats:sec>\n \n Material and methods<\/jats:title>\n \n We utilized the generically obese diabetic\n db\/db<\/jats:italic>\n mouse model for all experiments. Initial studies investigated both a dose and time course response. These results were then utilized to design a long\u2010term (5 week) treatment protocol. Mice were gavaged twice daily with 1 of 3 treatments: 200 mg\/kg BW TP113, an equivalent dose of metformin alone (70 mg\/kg BW) or water. Whole\u2010body insulin sensitivity was measured using the hyperinsulinaemic\u2010isoglycaemic clamp procedure in awake unrestrained mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We first confirmed that acute TP\u2010113 treatment raises PDX and IL\u20106 levels in skeletal muscle. We next tested the long\u2010term glucoregulatory effect of oral TP\u2010113 in obese diabetic\n db\/db<\/jats:italic>\n mice and compared its effect to an equivalent dose of metformin. A 5\u2010week oral treatment with TP\u2010113 reduced insulin resistance compared to both vehicle treatment and metformin alone, revealed by the determination of whole\u2010body insulin sensitivity for glucose disposal using the clamp technique. This insulin\u2010sensitizing effect was explained primarily by improvement of insulin action to suppress hepatic glucose production in TP\u2010113\u2010treated mice. These effects of TP\u2010113 were greater than that of an equivalent dose of metformin, indicating that TP\u2010113 increases metformin efficacy for reducing insulin resistance.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n We conclude that TP\u2010113 improves insulin sensitivity in obese diabetic mice through activation of the PDX\/IL\u20106 signaling axis in skeletal muscle and improved glucoregulatory action in the liver.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12818","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T08:29:50Z","timestamp":1481272190000},"page":"313-319","source":"Crossref","is-referenced-by-count":17,"title":["Treatment with a novel agent combining docosahexaenoate and metformin increases protectin DX and IL\u20106 production in skeletal muscle and reduces insulin resistance in obese diabetic\n db\/db<\/i>\n mice"],"prefix":"10.1111","volume":"19","author":[{"given":"Patricia L.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Axe Cardiologie Quebec Heart and Lung Research Institute Laval University Qu\u00e9bec Canada"},{"name":"Institute for Nutrition and Functional Foods Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Nachbar","sequence":"additional","affiliation":[{"name":"Axe Cardiologie Quebec Heart and Lung Research Institute Laval University Qu\u00e9bec Canada"},{"name":"Institute for Nutrition and Functional Foods Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Lachance","sequence":"additional","affiliation":[{"name":"Axe Cardiologie Quebec Heart and Lung Research Institute Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"St\u2010Pierre","sequence":"additional","affiliation":[{"name":"Axe Cardiologie Quebec Heart and Lung Research Institute Laval University Qu\u00e9bec Canada"},{"name":"Institute for Nutrition and Functional Foods Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Trottier","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de pharmacie Laboratory of Molecular Pharmacology \u2013 CHU de Qu\u00e9bec Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Barbier","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de pharmacie Laboratory of Molecular Pharmacology \u2013 CHU de Qu\u00e9bec Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Marette","sequence":"additional","affiliation":[{"name":"Axe Cardiologie Quebec Heart and Lung Research Institute Laval University Qu\u00e9bec Canada"},{"name":"Institute for Nutrition and Functional Foods Laval University Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05485"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3549"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.11.026"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508313330903"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2013.03.006"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13505"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8060329"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.33549\/physiolres.932715","article-title":"The effect of n\u20103 fatty acids on glucose homeostasis and insulin sensitivity","volume":"63","author":"Flachs 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