{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T03:54:24Z","timestamp":1787630064238,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["SAF2016-79794-R"],"award-info":[{"award-number":["SAF2016-79794-R"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and\/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Z\u00fccker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg\/kg body weight\/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p &gt; 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p &lt; 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model.<\/jats:p>","DOI":"10.3390\/pharmaceutics13101535","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T22:24:13Z","timestamp":1632695053000},"page":"1535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-3310","authenticated-orcid":false,"given":"Miguel","family":"Navarro-Alarc\u00f3n","sequence":"first","affiliation":[{"name":"Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9816-8618","authenticated-orcid":false,"given":"Fernando","family":"Gil-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Medicine, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-4858","authenticated-orcid":false,"given":"Cristina","family":"S\u00e1nchez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Nutrition and Food Science, Biomedical Research Centre, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-2584","authenticated-orcid":false,"given":"Juan","family":"Llopis","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Nutrition and Food Science, Biomedical Research Centre, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Villal\u00f3n-Mir","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Olmedo","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Medicine, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6243-7708","authenticated-orcid":false,"given":"Pablo","family":"Alarc\u00f3n-Guijo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biohealth Institute and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Biohealth Research Institute in Granada (ibs. GRANADA), University Hospital of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-6272","authenticated-orcid":false,"given":"Diego","family":"Salagre","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biohealth Institute and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Biohealth Research Institute in Granada (ibs. GRANADA), University Hospital of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Gaona","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biohealth Institute and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Biohealth Research Institute in Granada (ibs. GRANADA), University Hospital of Granada, 18016 Granada, Spain"},{"name":"Department of Teaching of the Nursing Career of the Catholic University of Santiago de Guayaquil, General Teaching Coordination Hospital of Specialties Dr. Teodoro Maldonado Carbo of Ecuador, Guayaquil 090615, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Paredes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biohealth Institute and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Biohealth Research Institute in Granada (ibs. GRANADA), University Hospital of Granada, 18016 Granada, Spain"},{"name":"Department of Docent, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Epidemiology and Tropical Medicine Services, Directorate of Naval Health, Navy of Ecuador, Guayaquil 090615, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0164-9648","authenticated-orcid":false,"given":"Ahmad","family":"Agil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biohealth Institute and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain"},{"name":"Biohealth Research Institute in Granada (ibs. GRANADA), University Hospital of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1039\/D0FO03213A","article-title":"Plant-derived melatonin from food: A gift of nature","volume":"12","author":"Cheng","year":"2021","journal-title":"Food Funct."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.smrv.2004.08.001","article-title":"The basic physiology and pathophysiology of melatonin","volume":"9","author":"Claustrat","year":"2005","journal-title":"Sleep Med. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Otamas, A., Grant, P.J., and Ajjan, R.A. (2020). Diabetes and atherothrombosis: The circadian rhythm and roleof melatonin in vascular protection. Diab. Vasc. Dis. 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