Effect of zinc supplementation on type 2 diabetes parameters and liver metallothionein expressions in Wistar rats.
ABSTRACT Zinc is a trace metal and acts as an active component of various enzymes. Zinc deficiency has been suggested to be associated with the development of diabetes. The present study investigated the role of zinc supplementation on prevention of diabetic conditions. A double-disease model mimicking hyperlipidemia and type 2 diabetes was created by applying high-fat diet and streptozotocin (STZ) to Wistar rats. We demonstrated that zinc supplementation improved symptoms of diabetes such as polydipsia and increased serum level of high-density lipoprotein cholesterol, indicating that zinc supplementation has a potential beneficial effect on diabetic conditions. The level of maldondialdehyde (MDA), an oxidative stress marker, was reduced in liver by zinc supplementation in high fat-fed rats with or without STZ injection. Meanwhile, we observed an increase in the expression of metallothioneins (MTs) in liver of rats treated with zinc. This suggests that the induction of MTs in liver, which has been shown to be important in scavenging free radicals, could be one of the underlying mechanisms of zinc supplementation on reducing MDA levels in liver. Finally, we found that zinc levels in liver were increased while there was no change in serum zinc levels, indicating that local zinc level might be a critical factor for the induction of MTs. Also, the level of MTs could potentially be an index of zinc bioavailability. Taken together, these results suggest that both zinc and MT could play an important role in balancing nutrition and metabolism to prevent diabetic development.
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ABSTRACT: Chronic hyperglycemia statue noticed in diabetes mellitus favors the manifestation of oxidative stress by increasing the production of reactive oxygen species and/or by reducing the antioxidant defense system activity. Zinc plays an important role in antioxidant defense in type 2 diabetic patients by notably acting as a cofactor of the superoxide dismutase enzyme, by modulating the glutathione metabolism and metallothionein expression, by competing with iron and copper in the cell membrane and by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase enzyme. Zinc also improves the oxidative stress in these patients by reducing chronic hyperglycemia. It indeed promotes phosphorylation of insulin receptors by enhancing transport of glucose into cells. However, several studies reveal changes in zinc metabolism in individuals with type 2 diabetes mellitus and controversies remain regarding the effect of zinc supplementation in the improvement of oxidative stress in these patients. Faced with the serious challenge of the metabolic disorders related to oxidative stress in diabetes along with the importance of antioxidant nutrients in the control of this disease, new studies may contribute to improve our understanding of the role played by zinc against oxidative stress and its connection with type 2 diabetes mellitus prognosis. This could serve as a prelude to the development of prevention strategies and treatment of disorders associated with this chronic disease.03/2015; 6(2):333-7. DOI:10.4239/wjd.v6.i2.333
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ABSTRACT: While it has long been known that zinc (Zn) is crucial for the proper growth and maintenance of normal biological functions, Zn has also been shown to exert insulin-mimetic and anti-diabetic effects. These insulin-like properties have been demonstrated in isolated cells, tissues, and different animal models of type 1 and type 2 diabetes. Zn treatment has been found to improve carbohydrate and lipid metabolism in rodent models of diabetes. In isolated cells, it enhances glucose transport, glycogen and lipid synthesis, and inhibits gluconeogenesis and lipolysis. The molecular mechanism responsible for the insulin-like effects of Zn compounds involves the activation of several key components of the insulin signaling pathways, which include the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B/Akt (PKB/Akt) pathways. However, the precise molecular mechanisms by which Zn triggers the activation of these pathways remain to be clarified. In this review, we provide a brief history of zinc, and an overview of its insulin-mimetic and anti-diabetic effects, as well as the potential mechanisms by which zinc exerts these effects.Journal of inorganic biochemistry 12/2012; 120C:8-17. DOI:10.1016/j.jinorgbio.2012.11.006 · 3.27 Impact Factor
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ABSTRACT: Pharmacological levels of zinc oxide can promote growth and health of weaning piglets, but the underlying molecular mechanisms are yet not fully understood. The aim of this study was to determine changes in the global hepatic protein expression in response to dietary zinc oxide in weaned piglets. Nine half-sib piglets were allocated to three dietary zinc treatment groups (50, 150, 2500 mg/kg dry matter). After 14 d, pigs were euthanized and liver samples taken. The increase in hepatic zinc concentration following dietary supplementation of zinc was accompanied by up-regulation of metallothionein mRNA and protein expression. Global hepatic protein profiles were obtained by two-dimensional difference gel electrophoresis following matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. A total of 15 proteins were differentially (P<0.05) expressed between groups receiving control (150 mg/kg) or pharmacological levels of zinc (2500 mg/kg) with 7 down- (e.g. arginase1, thiosulfate sulfurtransferase, HSP70) and 8 up-regulated (e.g. apolipoprotein AI, transferrin, C1-tetrahydrofolate synthase) proteins. Additionally, three proteins were differentially expressed with low zinc supply (50 mg/kg Zn) in comparison to the control diet. The identified proteins were mainly associated with functions related to cellular stress, transport, metabolism, and signal transduction. The differential regulation was evaluated at the mRNA level and a subset of three proteins of different functional groups was selected for confirmation by western blotting. The results of this proteomic study suggest that zinc affects important liver functions such as blood protein secretion, protein metabolism, detoxification and redox homeostasis, thus supporting the hypothesis of intermediary effects of pharmacological levels of zinc oxide fed to pigs.PLoS ONE 11/2013; 8(11):e81202. DOI:10.1371/journal.pone.0081202 · 3.53 Impact Factor