title: Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of zinc.
abstract: Disturbances of zinc homeostasis have been observed in several diseases, including diabetes mellitus. To further characterize the association between zinc and diabetes, we recruited 75 patients with type 1 or type 2 diabetes and 75 nondiabetic sex-/age-matched control subjects in order to analyze differences concerning human zinc transporter 8 (hZnT-8) expression, single nucleotide polymorphisms (SNPs) in the genes of hZnT-8 as well as metallothionein 1A and serum/intracellular zinc. Furthermore, we investigated the relation between insulin and zinc homeostasis in type 2 diabetic subjects and consolidated our results by in vitro analysis of the effect of insulin on cellular zinc status and by analysis of the modulation of insulin signal transduction by intracellular zinc homeostasis. Concerning the expression of hZnT-8 and the SNPs analyzed, we did not observe any differences between diabetic and control subjects. Serum zinc was significantly lower in diabetic patients compared to controls, and intracellular zinc showed the same tendency. Interestingly, type 2 diabetes patients treated with insulin displayed lower serum zinc compared to those not injecting insulin. In vitro analyses showed that insulin leads to an increase in intracellular zinc and that insulin signaling was enhanced by elevated intracellular zinc concentrations. In conclusion, we show that type 1 and type 2 diabetic patients suffer from zinc deficiency, and our results indicate that zinc supplementation may qualify as a potential treatment adjunct in type 2 diabetes by promoting insulin signaling, especially in zinc-deficient subjects.
authors.affiliation: Institute of Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Jansen
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenkranz
authors.forename: Silke
authors.initials: S
authors.lastname: Overbeck
authors.forename: Sabine
authors.initials: S
authors.lastname: Warmuth
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Wolfram
authors.initials: W
authors.lastname: Karges
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use*; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult; D015032:Zinc / Q000097:blood / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D003470:Culture Media; D007328:Insulin; C530099:MT1A protein, human; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D008668:Metallothionein; D051057:Proto-Oncogene Proteins c-akt; D015032:Zinc