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CC BY-NC-ND 4.0 · Journal of Social Health and Diabetes 2017; 05(02): 83-87
DOI: 10.1055/s-0038-1676241
Review Article
NovoNordisk Education Foundation

Role of zinc in insulin regulation and diabetes

Resham Raj Poudel
Department of Internal Medicine, Western Reserve Health Education, Youngstown, OH, USA
,
Yuvaraj Bhusal
1   Department of Internal Medicine, BPK Institute of Health Science, Dharan, Nepal
,
Biswaraj Tharu
2   Department of Internal Medicine, Institute of Medicine, Kathmandu, Nepal
,
Nisha Kusum Kafle
3   Department of Public Health, Institute of Medicine, Kathmandu, Nepal
› Author Affiliations
Further Information

Publication History

Received: 24 April 2017

Accepted: 02 May 2017

Publication Date:
23 November 2018 (online)

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Abstract

Zinc (Zn) affects glucose metabolism through insulin regulation and has potential implication in diabetes. Zn deficiency has not been proven in diabetes; however, observations of hyperzincuria, hypozincemia, and Zn malabsorption in diabetes indicate additional requirements for Zn. Mutation in Zn transporter 8 – a key protein in insulin secretion – has been associated with Type 2 diabetes. Zn supplementation in prediabetics and diabetics has been supported to improve plasma glucose, hemoglobin A1c (HbA1c), and lipids and potentially improve insulin sensitivity, reduce oxidative stress, and protect from renal damage.

Diabetes - hyperzincuria - hypozincemia - insulin - zinc
 

  • References

  • 1 Global Report on Diabetes. World Health Organization. 2017 Available from: http://www.who.int/diabetes/global-report/en [Last cited on 2017 Mar 23].
    PubMedGoogle Scholar
  • 2 Diabetes. Centers for Disease Control and Prevention. 2016 Available from: https://www.cdc.gov/chronicdisease/resources/publications/aag/diabetes.htm [Last cited on 2017 Mar 23].
    PubMedGoogle Scholar
  • 3 Office of Dietary Supplements – Zinc, National Institutes of Health, US Department of Health and Human Services. Available from: https://www.ods.od.nih.gov/factsheets/Zn-HealthProfessional/ [Last cited on 2017 Mar 23].
  • 4 Jansen J, Karges W, Rink L. Zinc and diabetes – Clinical links and molecular mechanisms. J Nutr Biochem 2009; 20: 399-417
    CrossrefPubMedGoogle Scholar
  • 5 Khan AR, Awan FR. Metals in the pathogenesis of type 2 diabetes. J Diabetes Metab Disord 2014; 13: 16
    CrossrefPubMedGoogle Scholar
  • 6 Solomons NW. Mild human zinc deficiency produces an imbalance between cell-mediated and humoral immunity. Nutr Rev 1998; 56 (01) (Pt 1) 27-28
    PubMedGoogle Scholar
  • 7 Prasad AS. Zinc: An overview. Nutrition 1995; 11 (Suppl. 01) 93-99
    Google Scholar
  • 8 Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 2006; 20: 3-18
    CrossrefPubMedGoogle Scholar
  • 9 Prasad AS, Beck FW, Grabowski SM, Kaplan J, Mathog RH. Zinc deficiency: Changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians 1997; 109: 68-77
    PubMedGoogle Scholar
  • 10 Chimienti F, Favier A, Seve M. ZnT-8, a pancreatic beta-cell-specific zinc transporter. Biometals 2005; 18: 313-317
    CrossrefPubMedGoogle Scholar
  • 11 Rink L, Gabriel P. Zinc and the immune system. Proc Nutr Soc 2000; 59: 541-552
    CrossrefPubMedGoogle Scholar
  • 12 Hambidge KM, Krebs NF. Zinc deficiency: A special challenge. J Nutr 2007; 137: 1101-1105
    CrossrefPubMedGoogle Scholar
  • 13 Van Wouwe JP. Clinical and laboratory assessment of zinc deficiency in Dutch children. A review. Biol Trace Elem Res 1995; 49: 211-225
    CrossrefPubMedGoogle Scholar
  • 14 King JC, Cousins RJ. Zinc. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. 10th . Baltimore MD: Lippincott Williams & Wilkins; 2005: 271-285
    Google Scholar
  • 15 Salgueiro MJ, Krebs N, Zubillaga MB, Weill R, Postaire E, Lysionek AE. et al. Zinc and diabetes mellitus: Is there a need of zinc supplementation in diabetes mellitus patients?. Biol Trace Elem Res 2001; 81: 215-228
    CrossrefPubMedGoogle Scholar
  • 16 Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr 1998; 17: 109-115
    CrossrefPubMedGoogle Scholar
  • 17 Rungby J. Zinc, zinc transporters and diabetes. Diabetologia 2010; 53: 1549-1551
    CrossrefPubMedGoogle Scholar
  • 18 Dunn MF. Zinc-ligand interactions modulate assembly and stability of the insulin hexamer – A review. Biometals 2005; 18: 295-303
    CrossrefPubMedGoogle Scholar
  • 19 Emdin SO, Dodson GG, Cutfield JM, Cutfield SM. Role of zinc in insulin biosynthesis. Some possible zinc-insulin interactions in the pancreatic B-cell. Diabetologia 1980; 19: 174-182
    CrossrefPubMedGoogle Scholar
  • 20 Sun W, Wang Y, Miao X, Wang Y, Zhang L, Xin Y. et al. Renal improvement by zinc in diabetic mice is associated with glucose metabolism signaling mediated by metallothionein and Akt, but not Akt2. Free Radic Biol Med 2014; 68: 22-34
    CrossrefPubMedGoogle Scholar
  • 21 Davidson HW, Wenzlau JM, O'Brien RM. Zinc transporter 8 (ZnT8) and ß cell function. Trends Endocrinol Metab 2014; 25: 415-424
    CrossrefPubMedGoogle Scholar
  • 22 Maret W. The function of zinc metallothionein: A link between cellular zinc and redox state. J Nutr 2000; 130 5S Suppl: 1455S-1458S
    CrossrefPubMedGoogle Scholar
  • 23 Smidt K, Jessen N, Petersen AB, Larsen A, Magnusson N, Jeppesen JB. et al. SLC30A3 responds to glucose-and zinc variations in beta-cells and is critical for insulin production and in vivo glucose-metabolism during beta-cell stress. PLoS One 2009; 4: e5684
    CrossrefPubMedGoogle Scholar
  • 24 Huang L. Zinc and its transporters, pancreatic ß-cells, and insulin metabolism. Vitam Horm 2014; 95: 365-390
    PubMedGoogle Scholar
  • 25 Kambe T. Molecular architecture and function of ZnT transporters. Curr Top Membr 2012; 69: 199-220
    PubMedGoogle Scholar
  • 26 Kim I, Kang ES, Yim YS, Ko SJ, Jeong SH, Rim JH. et al. A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion. Pharmacogenomics J 2011; 11: 191-198
    CrossrefPubMedGoogle Scholar
  • 27 Petersen AB, Smidt K, Magnusson NE, Moore F, Egefjord L, Rungby J. siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells. APMIS 2011; 119: 93-102
    CrossrefPubMedGoogle Scholar
  • 28 Tamaki M, Fujitani Y, Hara A, Uchida T, Tamura Y, Takeno K. et al. The diabetes-susceptible gene SLC30A8/ZnT8 regulates hepatic insulin clearance. J Clin Invest 2013; 123: 4513-4524
    CrossrefPubMedGoogle Scholar
  • 29 Wijesekara N, Dai FF, Hardy AB, Giglou PR, Bhattacharjee A, Koshkin V. et al. Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 2010; 53: 1656-1668
    CrossrefPubMedGoogle Scholar
  • 30 Tepaamorndech S, Kirschke CP, Pedersen TL, Keyes WR, Newman JW, Huang L. et al. Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activation and glucose uptake. FEBS J 2016; 283: 378-394
    CrossrefPubMedGoogle Scholar
  • 31 Liu Y, Batchuluun B, Ho L, Zhu D, Prentice KJ, Bhattacharjee A. et al. Characterization of zinc influx transporters (ZIPs) in pancreatic ß Cells: Roles in regulating cytosolic zinc homeostasis and insulin secretion. J Biol Chem 2015; 290: 18757-18769
    CrossrefPubMedGoogle Scholar
  • 32 Brender JR, Hartman K, Nanga RP, Popovych N, de la Salud Bea R, Vivekanandan S. et al. Role of zinc in human islet amyloid polypeptide aggregation. J Am Chem Soc 2010; 132: 8973-8983
    CrossrefPubMedGoogle Scholar
  • 33 Salamekh S, Brender JR, Hyung SJ, Nanga RP, Vivekanandan S, Ruotolo BT. et al. A two-site mechanism for the inhibition of IAPP amyloidogenesis by zinc. J Mol Biol 2011; 410: 294-306
    CrossrefPubMedGoogle Scholar
  • 34 ZNS-Clinical: Zinc, Serum. Mayo Medical Laboratories. Available from: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8620 [Last cited on 2017 Mar 23].
    Google Scholar
  • 35 ZNU-Clinical: Zinc 24 Hour. Mayo Medical Laboratories. Available from: http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8591 [Last cited on 2017 Mar 23; Last accessed on 2017 Jan 22].
    Google Scholar
  • 36 Garg VK, Gupta R, Goyal RK. Hypozincemia in diabetes mellitus. J Assoc Physicians India 1994; 42: 720-721
    PubMedGoogle Scholar
  • 37 Pidduck HG, Wren PJ, Evans DA. Hyperzincuria of diabetes mellitus and possible genetical implications of this observation. Diabetes 1970; 19: 240-247
    CrossrefPubMedGoogle Scholar
  • 38 Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr 2003; 133 (05) (Suppl. 01) 1485S-1489S
    CrossrefPubMedGoogle Scholar
  • 39 Diabetes. WHO Diabetes Fact Sheet. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/index.html [Last cited on 2017 Jan 22].
    Google Scholar
  • 40 Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, Jalbani N. et al. Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients. Biol Trace Elem Res 2008; 122: 1-18
    CrossrefPubMedGoogle Scholar
  • 41 Al-Maroof RA, Al-Sharbatti SS. Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Med J 2006; 27: 344-350
    PubMedGoogle Scholar
  • 42 Martín AM, Extremera BG, Soto MF, Martínez MR, Jiménez AG, Morales AG. et al. Zinc levels after intravenous administration of zinc sulphate in insulin-dependent diabetes mellitus patients. Klin Wochenschr 1991; 69: 640-644
    CrossrefPubMedGoogle Scholar
  • 43 Canfield WK, Hambidge KM, Johnson LK. Zinc nutriture in type I diabetes mellitus: Relationship to growth measures and metabolic control. J Pediatr Gastroenterol Nutr 1984; 3: 577-584
    CrossrefPubMedGoogle Scholar
  • 44 Heise CC, King JC, Costa FM, Kitzmiller JL. Hyperzincuria in IDDM women.Relationship to measures of glycemic control, renal function, and tissue catabolism. Diabetes Care 1988; 11: 780-786
    CrossrefPubMedGoogle Scholar
  • 45 Brun JF, Fons C, Fussellier M, Bardet L, Orsetti A. Urinary zinc and its relationships with microalbuminuria in type I diabetics. Biol Trace Elem Res 1992; 32: 317-323
    CrossrefPubMedGoogle Scholar
  • 46 Foster M, Petocz P, Samman S. Effects of zinc on plasma lipoprotein cholesterol concentrations in humans: A meta-analysis of randomised controlled trials. Atherosclerosis 2010; 210: 344-352
    CrossrefPubMedGoogle Scholar
  • 47 Gunasekara P, Hettiarachchi M, Liyanage C, Lekamwasam S. Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes. Diabetes Metab Syndr Obes 2011; 4: 53-60
    PubMedGoogle Scholar
  • 48 Parham M, Amini M, Aminorroaya A, Heidarian E. Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: A double blind, randomized, placebo-controlled, cross-over trial. Rev Diabet Stud 2008; 5: 102-109
    CrossrefPubMedGoogle Scholar
  • 49 Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi R, Constantine G, Katulanda P. Effects of zinc supplementation on diabetes mellitus: A systematic review and meta-analysis. Diabetol Metab Syndr 2012; 4: 13
    CrossrefPubMedGoogle Scholar
  • 50 Cruz KJ, Morais JB, de Oliveira AR, Severo JS, Marreiro DD. The effect of zinc supplementation on insulin resistance in obese subjects: A systematic review. Biol Trace Elem Res 2017; 176: 239-243
    CrossrefPubMedGoogle Scholar
  • 51 Islam MR, Attia J, Ali L, McEvoy M, Selim S, Sibbritt D. et al. Zinc supplementation for improving glucose handling in pre-diabetes: A double blind randomized placebo controlled pilot study. Diabetes Res Clin Pract 2016; 115: 39-46
    CrossrefPubMedGoogle Scholar
  • 52 Fiorentino TV, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des 2013; 19: 5695-5703
    CrossrefPubMedGoogle Scholar
  • 53 Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr 2003; 22: 316-321
    CrossrefPubMedGoogle Scholar
  • 54 Karatug A, Kaptan E, Bolkent S, Mutlu O, Yanardag R. Alterations in kidney tissue following zinc supplementation to STZ-induced diabetic rats. J Trace Elem Med Biol 2013; 27: 52-57
    CrossrefPubMedGoogle Scholar
  • 55 Tang Y, Yang Q, Lu J, Zhang X, Suen D, Tan Y. Zinc supplementation partially prevents renal pathological changes in diabetic rats. J Nutr Biochem 2010; 21: 237-246
    CrossrefPubMedGoogle Scholar
  • 56 Fernando J, Zhou S. The role of zinc in renal pathological changes in diabetic status. J Nutr Disord Ther 2015; 5: 165
    Google Scholar