Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep 22;13(10):1535.
doi: 10.3390/pharmaceutics13101535.

Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats

Miguel Navarro-Alarcón  1 , Fernando Gil-Hernández  2 , Cristina Sánchez-González  3 , Juan Llopis  3 , Marina Villalón-Mir  1 , Pablo Olmedo  2 , Pablo Alarcón-Guijo  4   5 , Diego Salagre  4   5 , Lorena Gaona  4   5   6 , Mario Paredes  4   5   7 , Ahmad Agil  4   5
Affiliations

Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats

Miguel Navarro-Alarcón et al. Pharmaceutics. .

Abstract

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 Zücker 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 > 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 < 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.

Keywords: copper; diabetic obese rat; melatonin; muscle and other organ and white adipose tissues; zinc.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Influence of melatonin supplementation in Zn levels of different organ tissues in male Zücker lean and diabetic fatty rats. (A) Liver Zn. (B) Skeletal muscle Zn. (C) Pancreas Zn. (D) Brain Zn. C–ZL: Control lean rats without melatonin; M–ZL: Lean rats with melatonin; C–ZDF: Control diabetic fatty rats without melatonin; M–ZDF: Diabetic fatty rats with melatonin; ZL: Zücker lean rats; ZDF: Zücker diabetic fatty rats. Values are means ± SEM (n = 10) of ratios of Zn levels. * p < 0.05; ** p < 0.01; *** p < 0.001 (Tukey post hoc test).
Figure 2
Figure 2
Influence of melatonin supplementation in Zn levels of white adipose tissues (WAT) in male Zücker lean and diabetic fatty rats. (A) Gonadal WAT Zn. (B) Renal WAT Zn. (C) Omentum WAT Zn. (D) Subcutaneous Zn. C–ZL: Control lean rats without melatonin; M–ZL: Lean rats with melatonin; C–ZDF: Control diabetic fatty rats without melatonin; M–ZDF: Diabetic fatty rats with melatonin; ZL: Zücker lean rats; ZDF: Zücker diabetic fatty rats. Values are means ± SEM (n = 10) of ratios of Zn levels. * p < 0.05; ** p < 0.01; *** p < 0.001 (Tukey post hoc test).
Figure 3
Figure 3
Influence of melatonin supplementation in Cu levels of different organ tissues in male Zücker lean and diabetic fatty rats. (A) Liver Cu. (B) Skeletal muscle Cu. (C) Pancreas Cu. (D) Brain Cu. C–ZL: Control lean rats without melatonin; M–ZL: Lean rats with melatonin; C–ZDF: Control diabetic fatty rats without melatonin; M–ZDF: Diabetic fatty rats with melatonin; ZL: Zücker lean rats; ZDF: Zücker diabetic fatty rats. Values are means ± SEM (n = 10) of ratios of Zn levels. * p < 0.05; ** p < 0.01; *** p < 0.001 (Tukey post hoc test).
Figure 4
Figure 4
Influence of melatonin supplementation in Cu levels of different white adipose tissues (WAT) in male Zücker lean and diabetic fatty rats. (A) Gonadal WAT Cu. (B) Renal WAT Cu. (C) Omentum WAT Cu. (D) Subcutaneous Cun. C–ZL: Control lean rats without melatonin; M–ZL: Lean rats with melatonin; C–ZDF: Control diabetic fatty rats without melatonin; M–ZDF: Diabetic fatty rats with melatonin; ZL: Zücker lean rats; ZDF: Zücker diabetic fatty rats. Values are means ± SEM (n = 10) of ratios of Zn levels (p > 0.05; Tukey post hoc test).
See this image and copyright information in PMC

References

    1. Cheng G., Ma T., Deng Z., Gutiérrez-Gamboa G., Ge Q., Xu P., Zhang Q., Zhang J., Meng J., Reiter R.J., et al. Plant-derived melatonin from food: A gift of nature. Food Funct. 2021;12:2829–2849. doi: 10.1039/D0FO03213A. - DOI - PubMed
    1. Claustrat B., Brun J., Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med. Rev. 2005;9:11–24. doi: 10.1016/j.smrv.2004.08.001. - DOI - PubMed
    1. Otamas A., Grant P.J., Ajjan R.A. Diabetes and atherothrombosis: The circadian rhythm and roleof melatonin in vascular protection. Diab. Vasc. Dis. Res. 2020:1–13. doi: 10.1177/1479164120920582. - DOI - PMC - PubMed
    1. De Bacquer D., Van Risseghem M., Clays E., Kittel F., De Backer G., Braeckman L. Rotating shift work and the metabolic syndrome: A prospective study. Int. J. Epidemiol. 2009;38:848–854. doi: 10.1093/ije/dyn360. - DOI - PubMed
    1. Pietroiusti A., Neri A., Somma G., Coppeta L., Iavicoli I., Bergamaschi A., Magrini A. Incidence of metabolic syndrome among night-shift healthcare workers. Occup. Environ. Med. 2010;67:54–57. doi: 10.1136/oem.2009.046797. - DOI - PubMed