The Role of Zinc Homeostasis in the Prevention of Diabetes Mellitus and Cardiovascular Diseases

Overview

Journal J Atheroscler Thromb

Date 2021 Jun 21

PMID 34148917

Citations 25

Authors

Yukinori Tamura

Affiliations

Soon will be listed here.

Abstract

Zinc is an essential micronutrient for human health and is involved in various biological functions, such as growth, metabolism, and immune function. In recent years, research on intracellular zinc dynamics has progressed, and it has become clear that zinc transporters strictly control intracellular zinc localization, zinc regulates the functions of various proteins and signal transduction pathways as a second messenger similar to calcium ions, and intracellular zinc dyshomeostasis is associated with impaired insulin synthesis, secretion, sensitivity, lipid metabolism, and vascular function. Numerous animal and human studies have shown that zinc deficiency may be associated with the risk factors for diabetes and cardiovascular diseases (CVDs) and zinc administration might be beneficial for the prevention and treatment of these diseases. Therefore, an understanding of zinc biology may help the establishment of novel strategies for the prevention and treatment of diabetes and CVDs. This review will summarize the current knowledge on the role of zinc homeostasis in the pathogenesis of diabetes and atherosclerosis and will discuss the potential of zinc in the prevention of these diseases.

Citing Articles

Improved linear growth after routine zinc supplementation in preterm very low birth weight infants.

Seidu T, Brion L, Heyne R, Brown L, Jacob T, Edwards A Pediatr Res. 2025; .

PMID: 40069483 DOI: 10.1038/s41390-025-03935-z.

Deciphering the role of metal ion transport-related genes in T2D pathogenesis and immune cell infiltration via scRNA-seq and machine learning.

Pu Z, Wang T, Lu Y, Wu Z, Chen Y, Luo Z Front Immunol. 2025; 15:1479166.

PMID: 39926598 PMC: 11802808. DOI: 10.3389/fimmu.2024.1479166.

Exploring the application of dietary antioxidant index for disease risk assessment: a comprehensive review.

Pourmontaseri H, Bazmi S, Sepehrinia M, Mostafavi A, Arefnezhad R, Homayounfar R Front Nutr. 2025; 11:1497364.

PMID: 39885868 PMC: 11781229. DOI: 10.3389/fnut.2024.1497364.

The role of zinc in the premature brain: functions, outcomes and future research perspectives.

Chamakioti M, Brion L, Viswanathan P, Lair C, Angelis D Front Pediatr. 2025; 12:1496846.

PMID: 39764159 PMC: 11700744. DOI: 10.3389/fped.2024.1496846.

Evaluation of the interface of metallic-coated biodegradable polymeric stents with prokaryotic and eukaryotic cells.

Sousa A, Branco R, Morais P, Pereira M, Amaro A, Piedade A Bioact Mater. 2024; 46:55-81.

PMID: 39737210 PMC: 11683264. DOI: 10.1016/j.bioactmat.2024.12.003.

References

Dunn M . Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review. Biometals. 2005; 18(4):295-303. DOI: 10.1007/s10534-005-3685-y. View

Haglund B, Ryckenberg K, Selinus O, Dahlquist G . Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc. Diabetes Care. 1996; 19(8):873-5. DOI: 10.2337/diacare.19.8.873. View

Samadi A, Isikhan S, Tinkov A, Lay I, Dosa M, Skalny A . Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus. Clin Nutr. 2019; 39(6):1849-1856. DOI: 10.1016/j.clnu.2019.07.026. View

Liu B, Cai Z, Zhou Y . Deficient zinc levels and myocardial infarction : association between deficient zinc levels and myocardial infarction: a meta-analysis. Biol Trace Elem Res. 2015; 165(1):41-50. DOI: 10.1007/s12011-015-0244-4. View

Ilouz R, Kaidanovich O, Gurwitz D, Eldar-Finkelman H . Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun. 2002; 295(1):102-6. DOI: 10.1016/s0006-291x(02)00636-8. View

Zhuang X, Pang X, Zhang W, Wu W, Zhao J, Yang H . Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction. Life Sci. 2011; 90(3-4):131-9. DOI: 10.1016/j.lfs.2011.10.025. View

Alissa E, Bahjri S, Ahmed W, Al-Ama N, Ferns G . Trace element status in Saudi patients with established atherosclerosis. J Trace Elem Med Biol. 2006; 20(2):105-14. DOI: 10.1016/j.jtemb.2005.10.004. View

Fernandez-Cao J, Warthon-Medina M, Moran V, Arija V, Doepking C, Lowe N . Dietary zinc intake and whole blood zinc concentration in subjects with type 2 diabetes versus healthy subjects: A systematic review, meta-analysis and meta-regression. J Trace Elem Med Biol. 2018; 49:241-251. DOI: 10.1016/j.jtemb.2018.02.008. View

Boesgaard T, Zilinskaite J, Vanttinen M, Laakso M, Jansson P, Hammarstedt A . The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study. Diabetologia. 2008; 51(5):816-20. DOI: 10.1007/s00125-008-0955-6. View

10.

Giacconi R, Muti E, Malavolta M, Cardelli M, Pierpaoli S, Cipriano C . A novel Zip2 Gln/Arg/Leu codon 2 polymorphism is associated with carotid artery disease in aging. Rejuvenation Res. 2008; 11(2):297-300. DOI: 10.1089/rej.2008.0671. View

11.

Simon S, Taylor C . Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood). 2001; 226(1):43-51. DOI: 10.1177/153537020122600107. View

12.

Mendes Garrido Abregu F, Gobetto M, Juriol L, Caniffi C, Elesgaray R, Tomat A . Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats. J Nutr Biochem. 2018; 56:89-98. DOI: 10.1016/j.jnutbio.2018.01.013. View

13.

Abdo A, Tran H, Hodge S, Beltrame J, Zalewski P . Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells. Biol Trace Elem Res. 2020; 199(6):2158-2171. DOI: 10.1007/s12011-020-02328-z. View

14.

Pilz S, Dobnig H, Winklhofer-Roob B, Renner W, Seelhorst U, Wellnitz B . Low serum zinc concentrations predict mortality in patients referred to coronary angiography. Br J Nutr. 2008; 101(10):1534-40. DOI: 10.1017/S0007114508084079. View

15.

Wijesekara N, Dai F, Hardy A, Giglou P, Bhattacharjee A, Koshkin V . Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia. 2010; 53(8):1656-68. PMC: 6101216. DOI: 10.1007/s00125-010-1733-9. View

16.

Bin B, Hojyo S, Hosaka T, Bhin J, Kano H, Miyai T . Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins. EMBO Mol Med. 2014; 6(8):1028-42. PMC: 4154131. DOI: 10.15252/emmm.201303809. View

17.

Oh K, Han H, Kim M, Koo S . CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis. BMB Rep. 2013; 46(12):567-74. PMC: 4133859. DOI: 10.5483/bmbrep.2013.46.12.248. View

18.

Singh R, GUPTA U, Mittal N, Niaz M, Ghosh S, Rastogi V . Epidemiologic study of trace elements and magnesium on risk of coronary artery disease in rural and urban Indian populations. J Am Coll Nutr. 1997; 16(1):62-7. DOI: 10.1080/07315724.1997.10718650. View

19.

Fernandez-Cao J, Warthon-Medina M, Moran V, Arija V, Doepking C, Serra-Majem L . Zinc Intake and Status and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Nutrients. 2019; 11(5). PMC: 6567047. DOI: 10.3390/nu11051027. View

20.

Cameron A, Anil S, Sutherland E, Harthill J, Rena G . Zinc-dependent effects of small molecules on the insulin-sensitive transcription factor FOXO1a and gluconeogenic genes. Metallomics. 2010; 2(3):195-203. DOI: 10.1039/b914984h. View