<i>SLC30A8</i> Nonsynonymous Variant Is Associated With Recovery Following Exercise and Skeletal Muscle Size and Strength

Sprouse, Courtney; Gordish‐Dressman, Heather; Orkunoglu-Suer, Funda E.; Lipof, Jason S.; Moeckel-Cole, Stephanie; Patel, Ronak; Adham, Kasra; Larkin, Justin S.; Hubal, Monica J.; Kearns, Amy K.; Clarkson, Priscilla M.; Thompson, Paul D.; Angelopoulos, Theodore J.; Gordon, Paul M.; Moyna, Niall M.; Pescatello, Linda S.; Visich, Paul S.; Zoeller, Robert F.; Hoffman, Eric P.; Tosi, Laura L.; Devaney, Joseph M.

doi:10.2337/db13-1150

Cited by 23 publications

(17 citation statements)

References 25 publications

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“…Thus, even though SLC30A8 is not expressed in liver or muscle, Tamaki and colleagues have shown that the SNP is associated with altered insulin clearance, as assessed by C-peptide/insulin ratios, consistent with their KO mouse data [82]. Similarly, Sprouse et al [99] reported that the SNP is associated with altered muscle function, perhaps suggesting that ZnT8 influences communication between β cells and other tissues. The fact that these fundamental questions remain to be addressed indicates that much still remains to be learned about ZnT8.…”

Section: Concluding Remarks and Future Perspectivessupporting

confidence: 53%

Zinc transporter 8 (ZnT8) and β cell function

Davidson

Wenzlau

O’Brien

2014

Trends in Endocrinology & Metabolism

135

120

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Human pancreatic β cells have exceptionally high zinc content. In β cells the highest zinc concentration is in insulin secretory granules, from which it is co-secreted with the hormone. Uptake of zinc into secretory granules is mainly mediated by zinc transporter 8 (ZnT8), the product of the SLC30A8 gene. The minor alleles of several single nucleotide polymorphisms (SNPs) in SLC30A8 are associated with decreased risk of type 2 diabetes (T2D), but the precise mechanisms underlying the protective effects remain uncertain. In this article we review current knowledge of the role of ZnT8 in maintaining zinc homeostasis in β cells, its role in glucose metabolism based on knockout mouse studies, and current theories regarding the link between ZnT8 function and T2D.

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Section: Concluding Remarks and Future Perspectivessupporting

confidence: 53%

Zinc transporter 8 (ZnT8) and β cell function

Davidson

Wenzlau

O’Brien

2014

Trends in Endocrinology & Metabolism

135

120

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“…Variants of single nucleotide polymorphism in ZnT8 gene have been associated with differences in muscle phenotype and function in men (Sprouse et al 2014). The positive relationship between ZIP7 gene expression and total physical activity level found in the current study may be reflective of the function of this particular zinc transporter in skeletal muscles.…”

Section: Discussionmentioning

confidence: 65%

Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults

et al. 2015

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The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n = 39) were randomised to zinc treatment (ZT), receiving 22 mg Zn/day (n = 19), or no treatment (NT) (n = 20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P = 0.025 and P = 0.016, respectively) compared to the NT group, specifically at Day 2 (40 ± 18 % increase from baseline, P = 0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2) = 0.54, P = 0.029); the change in ZIP1 expression emerged as a univariate predictor (P = 0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P = 0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r = 0.36, P = 0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

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“…This discrepancy requires further investigation. The SNP rs13266634 is implicated as a key determinant in humoral autoreactivity to ZnT8 (443) and is also related to a favorable cardiometabolic lipid profile in human immunodeficiency virus (HIV)/ hepatitis C virus-coinfected patients (322) and skeletal muscle strength and size (383).…”

Section: Single Nucleotide Polymorphism and Gene Dosage Effects Ofmentioning

confidence: 99%

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Kambe

Tsuji

Hashimoto

et al. 2015

Physiological Reviews

873

797

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Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly important. In metazoan, two zinc transporter families, Zn transporters (ZnT) and Zrt-, Irt-related proteins (ZIP) function in zinc mobilization of influx, efflux, and compartmentalization/ sequestration across biological membranes. During the last two decades, significant progress has been made in understanding the molecular properties, expression, regulation, and cellular and physiological roles of ZnT and ZIP transporters, which underpin the multifarious functions of zinc. Moreover, growing evidence indicates that malfunctioning zinc homeostasis due to zinc transporter dysfunction results in the onset and progression of a variety of diseases. This review summarizes current progress in our understanding of each ZnT and ZIP transporter from the perspective of zinc physiology and pathogenesis, discussing challenging issues in their structure and zinc transport mechanisms.

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SLC30A8 Nonsynonymous Variant Is Associated With Recovery Following Exercise and Skeletal Muscle Size and Strength

Cited by 23 publications

References 25 publications

Zinc transporter 8 (ZnT8) and β cell function

Zinc transporter 8 (ZnT8) and β cell function

Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

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