Störung des Zinkstoffwechsels bei Diabetes mellitus

Zusammenfassung

Als Bestandteil von mehr als tausend Proteinen hat Zink grundlegende und zahlreiche biologische Funktionen in Wachstum, Entwicklung und Stoffwechsel und ist damit eines der wichtigsten anorganischen Elemente des Lebens. In diesem Artikel weisen wir auf einen Zusammenhang zwischen Zinkstoffwechsel und Diabetes mellitus hin. Schwerpunkte unserer Betrachtung sind die Funktionen von Zink als Insulin-mimetische Substanz und in der Unterstützung des reduzierenden intrazellulären Milieus, das bei Diabetes durch oxidativen Stress gestört ist. Untersuchungen an Tier und Mensch belegen eine Störung des Zinkstoffwechsels bei Diabetes und vorbeugende sowie therapeutische Wirkungen von Zink; einen zuverlässigen klinischen Test, der es uns erlauben würde, Zinkmangelzustände zu erkennen, gibt es allerdings bislang nicht. Aussichten einer Therapie mit Zink und/oder Antioxidantien werden erörtert.

Summary

Zinc is one of the most important inorganic elements of life. Its biological functions in growth, development, and metabolism are based on its occurrence in at least one thousand zinc metalloproteins. Discoveries of insulin/zinc interactions, insulinomimetic effects of zinc, functions of zinc in controlling the cellular redox state, and oxidative stress in diabetes indicate specific roles of zinc in the pathobiochemistry of diabetes. A reliable clinical test to determine zinc deficiency states in diabetes is not available. Investigations in animals and humans support the conclusion that zinc metabolism is compromised in diabetes, and suggest preventive and therapeutic potentials of zinc and antioxidants.

Zink - Diabetes - Oxidativer Stress - Zufuhrempfehlungen

Zinc - diabetes - oxidative stress - recommended daily allowance (RDA)

Literatur

• 1 Maret W. Zinc Biochemistry, Physiology, and Homeostasis. Kluwer Academic Publishers 2001
• 2 Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.  Am J Hum Genet. 2002;  71 66-73
• 3 Kury S, Dreno B, Bezieau S. et al. . Identification of SLC39A4, a gene involved in acrodermatitis enteropathica.  Nat Genet. 2002;  31 239-240
• 4 Maret W, Vallee BL. Thiolate ligands in metallothionein confer redox activity on zinc clusters.  Proc Natl Acad Sci USA. 1998;  95 3478-3482
• 5 Kruse-Jarres JD, Rükgauer M. Trace Elements in diabetes mellitus. Peculiarities and clinical validity of determinations in blood cells.  J Trace Elem Med Biol. 2000;  14 21-27
• 6 Chausmer AB. Zinc, insulin and diabetes.  J Am Coll Nutr. 1998;  17 109-115
• 7 Oteiza PI, Clegg MS, Zago MP, Keen CL. Zinc deficiency induces oxidative stress and AP-1 activation in 3T3 cells.  Free Radic Biol Med. 2000;  28 1091-1099
• 8 Quarterman J, Mills CF, Humphries WR. The reduced secretion of, and sensitivity to insulin in zinc-deficient rats.  Biochem Biophys Res Commun. 1966;  25 354-358
• 9 Chimienti F, Devergnas S, Favier A, Seve M. Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.  Diabetes. 2004;  53 2330-2337
• 10 Keller SR. The insulin-regulated aminopeptidase: A companion and regulator of GLUT4.  Frontiers in Bioscience. 2003;  8 S410-S420
• 11 Maret W. Human Sorbitol Dehydrogenase - A Secondary Alcohol Dehydrogenase with Distinct Pathophysiological Roles. In: Weiner H, et al. (Eds.): Enzymology and Molecular Biology of Carbonyl Metabolism 6. New York: Plenum Press 1997: 383-393
• 12 Reiterer G, Toborek M, Hennig B. Peroxisome proliferator activated receptors alpha and gamma require zinc for their anti-inflammatory properties in porcine vascular endothelial cells.  J Nutr. 2004;  134 1711-1715
• 13 Tallman DL, Taylor CG. Potential interactions of zinc in the neuroendocrine-endocrine disturbances of diabetes mellitus type 2.  Can J Physiol Pharmacol. 1999;  77 919-933
• 14 Proceedings from the 4th International Biometals Symposium, Garmisch-Partenkirchen, 2004. »Zinc and Diabetes«, BioMetals, im Druck 2005
• 15 Beyersmann D, Haase H. Functions of zinc in signaling, proliferation and differentiation of mammalian cells.  BioMetals. 2001;  14 331-341
• 16 Tang X, Shay NF. Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes.  J Nutr. 2001;  131 1414-1420
• 17 Coulston L, Dandona P. Insulin-like effect of zinc on adipocytes.  Diabetes. 1980;  29 665-667
• 18 May JM, Contoreggi CS. The mechanism of the insulin-like effects of ionic zinc.  J Biol Chem. 1982;  257 4362-4368
• 19 Haase H, Maret W. Intracelluar zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling.  Exp Cell Res. 2003;  291 289-298
• 20 Haase H, Maret W. Fluctuations of cellular, available zinc modulate insulin signaling via inhibition of protein tyrosine phosphatases. J Trace Elem Biol Med; im Druck 2005
• 21 Haase H, Maret W. Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants. BioMetals; im Druck 2005
• 22 Zabolotny JM, Haj FG, Kim Y-B. et al. . Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action.  J Biol Chem. 2004;  279 24844-24851
• 23 Elchebly M, Payette P, Michaliszyn E. et al. . Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.  Science. 1999;  283 1544-1548
• 24 Zinker BA, Rondinone CM, Trevillyan JM. et al. . PTP 1B antisense oligonucleotide lowers PTP 1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice.  Proc Natl Acad Sci USA. 2002;  99 11357-11362
• 25 Briefel RR, Johnson CL. Secular trends in dietary intake in the United States.  Annu Rev Nutr. 2004;  24 401-431
• 26 Duchateau J, Delepesse G, Vrijens R, Collet H. Beneficial effects of oral zinc supplementation on the immune response of old people.  Am J Med. 1981;  70 1001-1004
• 27 Cakman I, Kirchner H, Rink L. Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons.  J Interferone Cytokine Res. 1997;  17 469-472
• 28 Rink L, Gabriel P. Extracellular and immunological actions of zinc.  BioMetals. 2001;  14 367-383
• 29 Karlsson MGE Faresjö, Ludvigsson J. Diminished TH1-like response to autoantigens in children with a high risk of developing type 1 diabetes.  Scand J Immunol. 2005;  61 173-179
• 30 Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection.  Am J Clin Nutr. 1998;  68 447S-463S
• 31 Finamore A, Roselli M, Merendino N. et al. . Zinc deficiency suppresses the development of oral tolerance in rats.  J Nutr. 2003;  133 191-198
• 32 Haglund B, Ryckenberg K, Selinus O, Dahlquist G. Evidence of a relationship between childhood-onset type 1 diabetes and low groundwater concentration of zinc.  Diab Care. 1996;  19 873-875
• 33 Zhao HX, Mold MD, Stenhouse EA. et al. . Drinking water composition and childhood-onset Type 1 diabetes mellitus in Devon and Cornwall, England.  Diabet Med. 2001;  18 709-717
• 34 Fraker PJ, King LE. Reprogramming of the immune system during zinc deficiency.  Annu Rev Nutr. 2004;  24 277-298
• 35 Schott-Ohly P, Lgssiar A, Partke HJ. et al. . Prevention of spontaneous and experimentally induced diabetes in mice with zinc sulfate-enriched drinking water is associated with activation and reduction of NF-kappa B and AP-1 in islets, respectively.  Exp Biol Med (Maywood). 2004;  229 1177-1185
• 36 Fischer C Walker, Black RE. Zinc and the risk for infectious disease.  Annu Rev Nutr. 2004;  24 255-275
• 37 Food and Nutrition Board and Institute of Medicine .Dietary Reference Intakes for Vitamin A, Vitamin K, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. ed. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Washington, DC: National Academy Press 2001: 12.1-12.47
• 38 Gibson RS. Content and bioavailability of trace elements in vegetarian diets.  Am J Clin Nutr. 1994;  59 1223S-1232S
• 39 Röhrig B, Anke M, Drobner C, Jaritz M, Holzinger S. Zinc intake of German adults with mixed and vegetarian diets.  Trace Elem Electrol. 1998;  15 81-86
• 40 Adolf T, Schneider R, Eberhardt W. et al. .Ergebnisse der Nationalen Verzehrstudie (1985-1988) über die Lebensmittel- und Nährstoffaufnahme in der Bundesrepublik Deutschland. In: Kübler W, Anders HJ, Heeschen W (Hrsg.): VERA-Schriftenreihe, Band XI. Niederkleen: Wissenschaftlicher Fachverlag Dr. Fleck 1995
• 41 Bundesinstitut für Risikobewertung: Risikobewertung von Zink. .In: Domke A, Großklaus R, Niemann B, et al. (Hrsg.): Verwendung von Mineralstoffen in Lebensmitteln. Toxikologische und ernährungsphysiologische Aspekte. Dahlem: Bfr-Hausdruckerei 2004: 253-260
• 42 Porea TJ, Belmont JW, Mahoney DH. Zinc-induced anemia and neutropenia in an adolescent.  J Pediatr. 2000;  136 688-690
• 43 Faber C, Gabriel P, Ibs KH, Rink L. Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response.  Bone Marrow Transplant. 2004;  33 1241-1246
• 44 Jarrard DF. Does zinc supplementation increase the risk of prostate cancer?.  Arch Ophthalmol. 2005;  123 102-103
• 45 Chen MD, Liou SJ, Lin PY, Yang VC, Alexander PS, Lin WH. Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice.  Biol Trace Elem Res. 1998;  61 303-311
• 46 Simon SF, Taylor CG. Dietary zinc supplementation attenuates hyperglycemia in db/db mice.  Exp Biol Med (Maywood). 2001;  226 43-51
• 47 Roussel AM, Kerkeni A, Zouari N. et al. . Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus.  J Am Coll Nutr. 2003;  22 316-321
• 48 Faure P, Benhamou PY, Perard A. et al. . Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation.  Eur J Clin Nutr. 1995;  49 282-288

Korrespondierender Autor