{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:22:34Z","timestamp":1774462954841,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T00:00:00Z","timestamp":1535673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Melatonin is a hormone synthesized mainly by the pineal gland, and secreted only at night. Melatonin has been proposed as a modulator of glucose metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we studied the metabolic effects of melatonin administration alone (s.c. 10 mg\/kg) or in combination with metformin (p.o. 300 mg\/kg), a widely used anti\u2010diabetic drug. These treatments were tested on glucose tolerance, insulin sensitivity and food intake in Zucker fatty rats (i.e., bearing a missense mutation in the leptin receptor gene) and high\u2010fat fed Sprague\u2010Dawley rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Melatonin alone or in combination did not significantly modify glucose tolerance in either model. Melatonin alone in high\u2010fat fed Sprague\u2010Dawley improved insulin sensitivity to the level of metformin. In addition, combined treatment further ameliorated insulin sensitivity (+13%), especially during the late phase of rising glycemia. The lack of similar effects in Zucker rats suggests an involvement of leptin signaling in mediating the positive effects of melatonin. Body mass gain in Sprague\u2010Dawley rats was decreased by both metformin, and combined metformin and melatonin. While melatonin alone did not markedly affect food intake, its combination with metformin led to a more pronounced anorexia (\u201017% food intake during the last week), as compared to metformin alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Melatonin improves the beneficial effects of metformin on insulin sensitivity and body mass gain in high\u2010fat fed Sprague\u2010Dawley rats. Therefore, the combination of melatonin and metformin could be beneficial to develop dual therapies to treat or delay type 2 diabetes associated with obesity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.39","type":"journal-article","created":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T01:20:02Z","timestamp":1535764802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high\u2010fat\u2010fed rats"],"prefix":"10.1002","volume":"1","author":[{"given":"Rosana F.","family":"Dantas\u2010Ferreira","sequence":"first","affiliation":[{"name":"Circadian Clocks &amp; Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene","family":"Raingard","sequence":"additional","affiliation":[{"name":"Circadian Clocks &amp; Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Dumont","sequence":"additional","affiliation":[{"name":"Circadian Clocks &amp; Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Schuster\u2010Klein","sequence":"additional","affiliation":[{"name":"ADIR\u2014SERVIER Research Group  Suresnes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Guardiola\u2010Lemaitre","sequence":"additional","affiliation":[{"name":"ADIR\u2014SERVIER Research Group  Suresnes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Pevet","sequence":"additional","affiliation":[{"name":"Circadian Clocks &amp; Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9416-9496","authenticated-orcid":false,"given":"Etienne","family":"Challet","sequence":"additional","affiliation":[{"name":"Circadian Clocks &amp; Metabolism team Institute of Cellular and Integrative Neurosciences Centre National de la Recherche Scientifique (CNRS) University of Strasbourg  Strasbourg France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703247104"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06246.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4175-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.03.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphysparis.2011.07.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1081\/CBI-100107511"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2016.05.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12137"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.00067.x"},{"issue":"4","key":"e_1_2_8_11_1","first-page":"995","article-title":"The regulation of insulin action in isolated adipocytes. 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