Zinc and Regulation of inflammatory cytokines: Implications for cardiometabolic disease

Nutrients

Volumn 4, Issue 7, 2012, Pages 676-694

  Foster, Meika ^a   Samman, Samir ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Atherosclerosis; Cytokines; Diabetes mellitus; Inflammation; Zinc

Indexed keywords

CYTOKINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; TUMOR NECROSIS FACTOR ALPHA; ZINC; ZINC TRANSPORTER;

ACUTE PHASE RESPONSE; ATHEROSCLEROSIS; CELL ACTIVATION; CELL CULTURE; CELL TYPE; CHRONIC DISEASE; CHRONIC INFLAMMATION; CYTOKINE PRODUCTION; DIABETES MELLITUS; DIET SUPPLEMENTATION; DOWN REGULATION; EXPERIMENTATION; HEART DISEASE; HUMAN; IN VITRO STUDY; INFLAMMATION; INFLAMMATORY DISEASE; INTRACELLULAR SPACE; METABOLIC DISORDER; METHODOLOGY; NUTRITION; PREVALENCE; REVIEW; UPREGULATION; ZINC BLOOD LEVEL; ZINC DEFICIENCY; ZINC METABOLISM;

EID: 84864331735     PISSN: 20726643     EISSN: None     Source Type: Journal    
DOI: 10.3390/nu4070676     Document Type: Review

References (103)

1. Prasad, A.S.; Halsted, J.A.; Nadimi, M. Syndrome of iron deficiency anaemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am. J. Med. 1961, 31, 532-546.
2. Vallee, B.L.; Falchuk, K.H. The biochemical basis of zinc physiology. Physiol. Rev. 1993, 73, 79-118.
3. Beyersmann, D.; Haase, H. Functions of zinc in signaling, proliferation and differentiation of mammalian cells. Biometals 2001, 14, 331-341.
4. Kre{ogonek}żel, A.; Maret, W. Zinc-buffering capacity of a eukaryotic cell at physiological pZn. J. Biol. Inorg. Chem. 2006, 11, 1049-1062.
5. Frederickson, C.J.; Koh, J.Y.; Bush, A.I. The neurobiology of zinc in health and disease. Nat. Rev. Neurosci. 2005, 6, 449-462.
6. Ezzati, M.; Lopez, A.D.; Rodgers, A.; Vander Hoorn, S.; Murray, C.J.L.; Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of disease. Lancet 2002, 360, 1347-1360.
7. Wuehler, S.E.; Peerson, J.M.; Brown, K.H. Use of national food balance data to estimate the adequacy of zinc in national food supplies: Methodology and regional estimates. Public Health Nutr. 2005, 8, 812-819.
8. Prasad, A.S. Zinc in human health: Effect of zinc on immune cells. Mol. Med. 2008, 14, 353-357.
9. Kruse-Jarres, J.D. The significance of zinc for humoral and cellular immunity. J. Trace Elem. Electrolytes Health Dis. 1989, 3, 1-8.
10. Abbas, A.K.; Lichtman, A.H. Cellular and Molecular Immunology, 5th ed.; Elsevier Saunders: Philadelphia, PA, USA, 2005.
11. Zhou, X.; Fragala, M.S.; McElhaney, J.E.; Kuchel, G.A. Conceptual and methodological issues relevant to cytokine and inflammatory marker measurements in clinical research. Curr. Opin. Clin. Nutr. Metab. Care 2010, 13, 541-547.
12. Medzhitov, R. Inflammation 2010: New adventures of an old flame. Cell 2010, 140, 771-776.
13. Nathan, C.; Ding, A. Nonresolving inflammation. Cell 2010, 140, 871-882.
14. Krebs, N.E.; Hambidge, K.M. Zinc metabolism and homeostasis: The application of tracer techniques to human zinc physiology. Biometals 2001, 14, 397-412.
15. Foster, M.; Samman, S. Zinc and redox signaling: Perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid. Redox Signal. 2010, 13, 1549-1573.
16. Prasad, A.S. Zinc and immunity. Mol. Cell. Biochem. 1998, 188, 63-69.
17. Besecker, B.Y.; Exline, M.C.; Hollyfield, J.; Phillips, G.; Disilvestro, R.A.; Wewers, M.D.; Knoell, D.L. A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am. J. Clin. Nutr. 2011, 93, 1356-1364.
18. Egefjord, L.; Jensen, J.L.; Bang-Berthelsen, C.H.; Petersen, A.B.; Smidt, K.; Schmitz, O.; Karlsen, A.E.; Pociot, F.; Chimienti, F.; Rungby, J.; Magnusson, N.E. Zinc transporter gene expression is regulated by pro-inflammatory cytokines: A potential role for zinc transporters in beta-cell apoptosis? BMC Endocr. Disord. 2009, 9, 7.
19. Lang, C.; Murgia, C.; Leong, M.; Tan, L.W.; Perozzi, G.; Knight, D.; Ruffin, R.; Zalewski, P. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 292, L577-L584.
20. Liuzzi, J.P.; Lichten, L.A.; Rivera, S.; Blanchard, R.K.; Aydemir, T.B.; Knutson, M.D.; Ganz, T.; Cousins, R.J. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc. Natl. Acad. Sci. USA 2005, 102, 6843-6848.
21. Cousins, R.J.; Leinart, A.S. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 1988, 2, 2884-2890.
22. De, S.K.; McMaster, M.T.; Andrews, G.K. Endotoxin induction of murine metallothionein gene expression. J. Biol. Chem. 1990, 265, 15267-15274.
23. Lichten, L.A.; Cousins, R.J. Mammalian zinc transporters: Nutritional and physiological regulation. Annu. Rev. Nutr. 2009, 29, 153-176.
24. Kim, S.; Watanabe, K.; Shirahata, T.; Watarai, M. Zinc uptake system (znuA locus) of Brucella abortus is essential for intracellular survival and virulence in mice. J. Vet. Med. Sci. 2004, 66, 1059-1063.
25. Gaetke, L.M.; McClain, C.J.; Talwalkar, R.T.; Shedlofsky, S.I. Effects of endotoxin on zinc metabolism in human volunteers. Am. J. Physiol. 1997, 272, E952-E956.
26. Young, B.; Ott, L.; Kasarskis, E.; Rapp, R.; Moles, K.; Dempsey, R.J.; Tibbs, P.A.; Kryscio, R.; McClain, C. Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury. J. Neurotrauma 1996, 13, 25-34.
27. Hotamisligil, G.S. Inflammation and metabolic disorders. Nature 2006, 444, 860-867.
28. Costarelli, L.; Muti, E.; Malavolta, M.; Cipriano, C.; Giacconi, R.; Tesei, S.; Piacenza, F.; Pierpaoli, S.; Gasparini, N.; Faloia, E.; et al. Distinctive modulation of inflammatory and metabolic parameters in relation to zinc nutritional status in adult overweight/obese subjects. J. Nutr. Biochem. 2010, 21, 432-437.
29. Prasad, A.S.; Beck, F.W.; Grabowski, S.M.; Kaplan, J.; Mathog, R.H. 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.
30. Beck, F.W.; Li, Y.; Bao, B.; Prasad, A.S.; Sarkar, F.H. Evidence for reprogramming global gene expression during zinc deficiency in the HUT-78 cell line. Nutrition 2006, 22, 1045-1056.
31. Prasad, A.S.; Bao, B.; Beck, F.W.J.; Sarkar, F.H. Correction of interleukin-2 gene expression by in vitro zinc addition to mononuclear cells from zinc-deficient human subjects: A specific test for zinc deficiency in humans. Transl. Res. 2006, 148, 325-333.
32. Pinna, K.; Kelley, D.S.; Taylor, P.C.; King, J.C. Immune functions are maintained in healthy men with low zinc intake. J. Nutr. 2002, 132, 2033-2036.
33. Wieringa, F.T.; Dijkhuizen, M.A.; West, C.E.; van der Ven-Jongekrijg, J.; van der Meer, J.W.; Muhilal. Reduced production of immunoregulatory cytokines in vitamin A-and zinc-deficient Indonesian infants. Eur. J. Clin. Nutr. 2004, 58, 1498-1504.
34. Bao, B.; Prasad, A.S.; Beck, F.W.J.; Snell, D.; Suneja, A.; Sarkar, F.H.; Doshi, N.; Fitzgerald, J.T.; Swerdlow, P. Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients. Transl. Res. 2008, 152, 67-80.
35. Prasad, A.S.; Beck, F.W.J.; Bao, B.; Fitzgerald, J.T.; Snell, D.C.; Steinberg, J.D.; Cardozo, L.J. Zinc supplementation decreases incidence of infections in the elderly: Effect of zinc on generation of cytokines and oxidative stress. Am. J. Clin. Nutr. 2007, 85, 837-844.
36. Bao, B.; Prasad, A.S.; Beck, F.W.J.; Fitzgerald, J.T.; Snell, D.; Bao, G.W.; Singh, T.; Cardozo, L.J. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: A potential implication of zinc as an atheroprotective agent. Am. J. Clin. Nutr. 2010, 91, 1634-1641.
37. Prasad, A.S.; Bao, B.; Beck, F.W.J.; Kucuk, O.; Sarkar, F.H. Antioxidant effect of zinc in humans. Free Radic. Biol. Med. 2004, 37, 1182-1190.
38. Raqib, R.; Roy, S.K.; Rahman, M.J.; Azim, T.; Ameer, S.S.; Chisti, J.; Andersson, J. Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis. Am. J. Clin. Nutr. 2004, 79, 444-450.
39. Sandstead, H.H.; Prasad, A.S.; Penland, J.G.; Beck, F.W.J.; Kaplan, J.; Egger, N.G.; Alcock, N.W.; Carroll, R.M.; Ramanujam, V.M.S.; Dayal, H.H.; et al. Zinc deficiency in Mexican American children: Influence of zinc and other micronutrients on T cells, cytokines, and antiinflammatory plasma proteins. Am. J. Clin. Nutr. 2008, 88, 1067-1073.
40. Aydemir, T.B.; Blanchard, R.K.; Cousins, R.J. Zinc supplementation of young men alters metallothionein, zinc transporter, and cytokine gene expression in leukocyte populations. Proc. Natl. Acad. Sci. USA 2006, 103, 1699-1704.
41. Kahmann, L.; Uciechowski, P.; Warmuth, S.; Plümäkers, B.; Gressner, A.M.; Malavolta, M.; Mocchegiani, E.; Rink, L. Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res. 2008, 11, 227-237.
42. Mariani, E.; Cattini, L.; Neri, S.; Malavolta, M.; Mocchegiani, E.; Ravaglia, G.; Facchini, A. Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: Relationship with zinc status. Biogerontology 2008, 7, 449-459.
43. Mocchegiani, E.; Giacconi, R.; Costarelli, L.; Muti, E.; Cipriano, C.; Tesei, S.; Pierpaoli, S.; Giuli, C.; Papa, R.; Marcellini, F.; et al. Zinc deficiency and IL-6-174G/C polymorphism in old people from different European countries: Effect of zinc supplementation. ZINCAGE study. Exp. Gerontol. 2008, 43, 433-444.
44. Kara, E.; Ozal, M.; Gunay, M.; Kilic, M.; Baltaci, A.K.; Mogulkoc, R. Effects of exercise and zinc supplementation on cytokine release in young wrestlers. Biol. Trace Elem. Res. 2011, 143, 1435-1440.
45. Bao, B.; Prasad, A.S.; Beck, F.W.; Bao, G.W.; Singh, T.; Ali, S.; Sarkar, F.H. Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells. Biochem. Biophys. Res. Commun. 2011, 407, 703-707.
46. Hayashi, K.; Ishizuka, S.; Yokoyama, C.; Hatae, T. Attenuation of interferon-gamma mRNA expression in activated Jurkat T cells by exogenous zinc via down-regulation of the calcium-independent PKC-AP-1 signaling pathway. Life Sci. 2008, 83, 6-11.
47. Prasad, A.S.; Bao, B.; Beck, F.W.J.; Sarkar, F.H. Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB. Nutrition 2011, 27, 816-823.
48. Freitas, M.; Fernandes, E. Zinc, cadmium and nickel increase the activation of NF-κB and the release of cytokines from THP-1 monocytic cells. Metallomics 2011, 3, 1238-1243.
49. Tsou, T.C.; Chao, H.R.; Yeh, S.C.; Tsai, F.Y.; Lin, H.J. Zinc induces chemokine and inflammatory cytokine release from human promonocytes. J. Hazard. Mater. 2011, 196, 335-341.
50. Metz, C.H.; Schröder, A.K.; Overbeck, S.; Kahmann, L.; Plümäkers, B.; Rink, L. T-helper type 1 cytokine release is enhanced by in vitro zinc supplementation due to increased natural killer cells. Nutrition 2007, 23, 157-163.
51. Poleganov, M.A.; Pfeilschifter, J.; Mühl, H. Expanding extracellular zinc beyond levels reflecting the albumin-bound plasma zinc pool potentiates the capability of IL-1β, IL-18, and IL-12 to act as IFN-γ-inducing factors on PBMC. J. Interferon Cytokine Res. 2007, 27, 997-1001.
52. Chang, K.L.; Hung, T.C.; Hsieh, B.S.; Chen, Y.H.; Chen, T.F.; Cheng, H.L. Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells. Nutrition 2006, 22, 465-474.
53. Von Bülow, V.; Rink, L.; Haase, H. Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF-alpha and IL-1 beta production in monocytes by elevation of guanosine 3′,5′-cyclic monophosphate. J. Immunol. 2005, 175, 4697-4705.
54. Wellinghausen, N.; Martin, M.; Rink, L. Zinc inhibits interleukin-1-dependent T cell stimulation. Eur. J. Immunol. 1997, 27, 2529-2535.
55. Driessen, C.; Hirv, K.; Wellinghausen, N.; Kirchner, H.; Rink, L. Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide-induced production of IFN-gamma and IL-1 beta by human mononuclear cells. J. Leukoc. Biol. 1995, 57, 904-908.
56. Scuderi, P. Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. Cell. Immunol. 1990, 126, 391-405.
57. Prasad, A.S. Zinc: Mechanisms of host defense. J. Nutr. 2007, 137, 1345-1349.
58. Beck, F.W.J.; Prasad, A.S.; Kaplan, J.; Fitzgerald, J.T.; Brewer, G.J. Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am. J. Physiol. 1997, 272, E1002-E1007.
59. Tapazoglou, E.; Prasad, A.S.; Hill, G.; Brewer, G.J.; Kaplan, J. Decreased natural killer cell activity in zinc deficient subjects with sickle cell disease. J. Lab. Clin. Med. 1985, 105, 19-22.
60. Fantone, J.C.; Ward, P.A. Polymorphonuclear leukocyte-mediated cell and tissue injury: Oxygen metabolites and their relations to human disease. Hum. Pathol. 1985, 16, 973-978.
61. Scapini, P.; Lapinet-Vera, J.A.; Gasperini, S.; Calzetti, F.; Bazzoni, F.; Cassatella, M.A. The neutrophil as a cellular source of chemokines. Immunol. Rev. 2000, 177, 195-203.
62. Finamore, A.; Massimi, M.; Conti Devirgiliis, L.; Mengheri, E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J. Nutr. 2008, 138, 1664-1670.
63. Gavella, M.; Lipovac, V.; Car, A. In vitro effect of zinc on superoxide anion production by polymorphonuclear leukocytes of diabetic patients. Acta Diabetol. 2000, 37, 135-137.
64. Siminiak, T.; Flores, N.A.; Sheridan, D.J. Neutrophil interactions with endothelium and platelets: Possible role in the development of cardiovascular injury. Eur. Heart J. 1995, 16, 160-170.
65. Verstrepen, L.; Bekaert, T.; Chau, T.L.; Tavernier, J.; Chariot, A.; Beyaert, R. TLR-4, IL-1R and TNF-R signaling to NF-κB: Variations on a common theme. Cell. Mol. Life Sci. 2008, 65, 2964-2978.
66. Bao, B.; Prasad, A.; Beck, F.W.; Suneja, A.; Sarkar, F. Toxic effect of zinc on NF-kappaB, IL-2, IL-2 receptor alpha, and TNF-alpha in HUT-78 (Th(0) cells. Toxicol. Lett. 2006, 166, 222-228.
67. von Bülow, V.; Dubben, S.; Engelhardt, G.; Hebel, S.; Plümäkers, B.; Heine, H.; Rink, L.; Haase, H. Zinc-dependent suppression of TNF-α production is mediated by protein kinase A-induced inhibition of Raf-1, IκB Kinase β, and NF-κB. J. Immunol. 2007, 179, 4180-4186.
68. Song, H.Y.; Rothe, M.; Goeddel, D.V. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-κB activation. Proc. Natl. Acad. Sci. USA 1996, 93, 6721-6725.
69. Kim, Y.M.; Cao, D.; Reed, W.; Wu, W.; Jaspers, I.; Tal, T.; Bromberg, P.A.; Samet, J.M. Zn2+-induced NF-κB-dependent transcriptional activity involves site-specific p65/RelA phosphorylation. Cell. Signal. 2007, 19, 538-546.
70. Bao, S.; Liu, M.J.; Lee, B.; Besecker, B.; Lai, J.P.; Guttridge, D.C.; Knoell, D.L. Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-κB. Am. J. Physiol. Lung Cell. Mol. Physiol. 2010, 298, L744-L754.
71. Dinarello, C.A. Immunological and inflammatory functions of the Interleukin-1 family. Annu. Rev. Immunol. 2009, 27, 519-550.
72. Bogdan, C. Nitric oxide and the immune response. Nat. Immunol. 2001, 2, 907-916.
73. Zou, M.H.; Shi, C.; Cohen, R.A. Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J. Clin. Invest. 2002, 109, 817-826.
74. Thomas, S.R.; Witting, P.K.; Drummond, G.R. Redox control of endothelial function and dysfunction: Molecular mechanisms and therapeutic opportunities. Antioxid. Redox Signal. 2008, 10, 1713-1765.
75. Xu, J.; Xie, Z.; Reece, R.; Pimental, D.; Zou, M.H. Uncoupling of endothelial nitric oxidase synthase by hypochlorous acid. Role of NAD(P)H oxidase-derived superoxide and peroxynitrite. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2688-2695.
76. Azumi, H.; Inoue, N.; Takeshita, S.; Rikitake, Y.; Kawashima, S.; Hayashi, Y.; Itoh, H.; Yokoyama, M. Expression of NADH/NADPH oxidase p22phox in human coronary arteries. Circulation 1999, 100, 1494-1498.
77. Matsunaga, Y.; Kawai, Y.; Kohda, Y.; Gemba, M. Involvement of activation of NADPH oxidase and extracellular signal-regulated kinase (ERK) in renal cell injury induced by zinc. J. Toxicol. Sci. 2005, 30, 135-144.
78. Foster, M.; Samman, S. Zinc and Atherosclerosis: Clinical Observations and Potential Mechanisms. In Zinc and Human Health: Biomedical and Health Research; Rink, L., Ed.; IOS Press: Amsterdam, The Netherlands, 2011; Volume 76, pp. 347-372.
79. Rowe, D.J.; Bobilya, D.J. Albumin facilitates zinc acquisition by endothelial cells. Proc. Soc. Exp. Biol. Med. 2000, 224, 178-186.
80. Beattie, J.H.; Kwun, I.S. Is zinc deficiency a risk factor for atherosclerosis? Br. J. Nutr. 2004, 91, 177-181.
81. Hughes, S.; Samman, S. The effect of zinc supplementation in humans on plasma lipids, antioxidant status, and thrombogenesis. J. Am. Coll. Nutr. 2006, 25, 285-291.
82. 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.
83. Meerarani, P.; Ramadass, P.; Toborek, M.; Bauer, H.C.; Bauer, H.; Hennig, B. Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha. Am. J. Clin. Nutr. 2000, 71, 81-87.
84. Wiseman, D.A.; Wells, S.M.; Hubbard, M.; Welker, J.E.; Black, S.M. Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 292, L165-L177.
85. Hennig, B.; Meerarani, P.; Toborek, M.; McClain, C.J. Antioxidant-like properties of zinc in activated endothelial cells. J. Am. Coll. Nutr. 1999, 18, 152-158.
86. Bourcier, T.; Sukhova, G.; Libby, P. The nuclear factor kB signaling pathway participates in dysregulation of vascular smooth muscle cells in vitro and in human atherosclerosis. J. Biol. Chem. 1997, 272, 15817-15824.
87. De Martin, R.; Hoeth, M.; Hofer-Warbinek, R.; Schmid, J.A. The transcription factor NF-κB and the regulation of vascular cell function. Arterioscler. Thromb. Vasc. Biol. 2000, 20, e83-e88.
88. Pasterkamp, G.; van Keulen, J.K.; de Kleijn, D.P.V. Role of Toll-like receptor 4 in the initiation and progression of atherosclerotic disease. Eur. J. Clin. Invest. 2004, 34, 328-334.
89. Cortese-Krott, M.M.; Suschek, C.V.; Wetzel, W.; Kröncke, K.D.; Kolb-Bachofen, V. Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione. Am. J. Physiol. Cell Physiol. 2009, 296, 811-820.
90. Donath, M.Y.; Størling, J.; Maedler, K.; Mandrup-Poulsen, T. Inflammatory mediators and islet beta-cell failure: A link between type 1 and type 2 diabetes. J. Mol. Med. 2003, 81, 455-470.
91. Maedler, K.; Sergeev, P.; Ris, F.; Oberholzer, J.; Joller-Jemelka, H.I.; Spinas, G.A.; Kaiser, N.; Halban, P.A.; Donath, M.Y. Glucose-induced beta cell production of IL1-beta contributes to glucotoxicity in human pancreatic islets. J. Clin. Invest. 2002, 110, 851-860.
92. Ehses, J.A.; Perren, A.; Eppler, E.; Ribaux, P.; Pospisilik, J.A.; Maor-Cahn, R.; Gueripel, X.; Ellingsgaard, H.; Schneider, M.K.; Biollaz, G.; et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 2007, 56, 2356-2370.
93. Spranger, J.; Kroke, A.; Möhlig, M.; Hoffman, K.; Bergmann, M.M.; Ristow, M.; Boeing, H.; Pfeiffer, A.F. Inflammatory cytokines and the risk to develop type 2 diabetes: Results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003, 52, 812-817.
94. Donath, M.Y.; Böni-Schnetzler, M.; Ellingsgaard, H.; Halban, P.A.; Ehses, J.A. Cytokine production by islets in health and diabetes: Cellular origin, regulation and function. Trends Endocrinol. Metab. 2010, 21, 261-267.
95. Arai, K.; Iizuka, S.; Tada, Y.; Oikawa, K.; Taniguchi, N. Increase in the glucosylated form of erythrocyte Cu-Zn-superoxide dismutase in diabetes and close association of the nonenzymatic glucosylation with the enzyme activity. Biochim. Biophys. Acta 1987, 924, 292-296.
96. King, G.L.; Loeken, M.R. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem. Cell Biol. 2004, 122, 333-338.
97. Gupta, R.; Garg, V.K.; Mathur, D.K.; Goyal, R.K. Oral zinc therapy in diabetic neuropathy. J. Assoc. Physicians India 1998, 46, 939-942.
98. Kajanachumpol, S.; Srisurapanon, S.; Supanit, I.; Roongpisuthipong, C.; Apibal, S. Effect of zinc supplementation on zinc status, copper status and cellular immunity in elderly patients with diabetes mellitus. J. Med. Assoc. Thail. 1995, 78, 344-349.
99. Samman, S.; Foster, M.; Capdor, J.; Stathakis, E. Zinc, diabetes mellitus and cardiovascular disease in humans: A critical appraisal. In Proceedings of International Society for Zinc Biology Conference, Melbourne, Australia, 15-19 January 2012; Abstract #71.
100. Wellinghausen, N.; Kirchner, H.; Rink, L. The immunobiology of zinc. Immunol. Today 1997, 18, 519-521.
101. Cave, A.C.; Brewer, A.C.; Narayanapanicker, A.; Ray, R.; Grieve, D.J.; Walker, S.; Shah, A.M. NADPH oxidases in cardiovascular health and disease. Antioxid. Redox Signal. 2006, 8, 691-728.
102. Ibs, K.H.; Rink, L. Zinc-altered immune function. J. Nutr. 2003, 133, 1452S-1456S.
103. Samman, S. Dietary versus cellular zinc: The antioxidant paradox. Free Radic. Biol. Med. 1993, 14, 95-96.