Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of zinc

被引：94

作者：

Jansen, Judith ^{[1
]}

Rosenkranz, Eva ^{[1
]}

Overbeck, Silke ^{[1
]}

Warmuth, Sabine ^{[2
]}

Mocchegiani, Eugenio ^{[3
]}

Giacconi, Robertina ^{[3
]}

Weiskirchen, Ralf ^{[4
]}

Karges, Wolfram ^{[5
]}

Rink, Lothar ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Inst Immunol, Fac Med, D-52074 Aachen, Germany

[2] Rhein Westfal TH Aachen, Univ Employee Hlth Off, D-52074 Aachen, Germany

[3] Res Dept INRCA, Sect Nutr Immun & Ageing, Immunol Ctr, I-60121 Ancona, Italy

[4] Rhein Westfal TH Aachen, Fac Med, Inst Clin Chem & Pathobiochem, D-52074 Aachen, Germany

[5] Rhein Westfal TH Aachen, Fac Med, Div Endocrinol & Diabet, D-52074 Aachen, Germany

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2012年 / 23卷 / 11期

关键词：

Zinc; Diabetes mellitus; Zinc transporter; Single nucleotide polymorphism; Insulin signaling; Metallothionein; GENOME-WIDE ASSOCIATION; ALTERED IMMUNE FUNCTION; PANCREATIC BETA-CELLS; TRANSPORTER ZNT8; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; RISK LOCI; DOWN-REGULATION; CELLULAR ZINC; PLASMA ZINC;

D O I：

10.1016/j.jnutbio.2011.09.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：1458 / 1466

页数：9

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