The Zinc Transporter, Slc39a7 (Zip7) is Implicated in Glycaemic Control in Skeletal Muscle Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Nov 23

PMID 24265765

Citations 38

Authors

Stephen A Myers

Alex Nield

Guat-Siew Chew

Mark A Myers

Affiliations

Soon will be listed here.

Abstract

Dysfunctional zinc signaling is implicated in disease processes including cardiovascular disease, Alzheimer's disease and diabetes. Of the twenty-four mammalian zinc transporters, ZIP7 has been identified as an important mediator of the 'zinc wave' and in cellular signaling. Utilizing siRNA targeting Zip7 mRNA we have identified that Zip7 regulates glucose metabolism in skeletal muscle cells. An siRNA targeting Zip7 mRNA down regulated Zip7 mRNA 4.6-fold (p = 0.0006) when compared to a scramble control. This was concomitant with a reduction in the expression of genes involved in glucose metabolism including Agl, Dlst, Galm, Gbe1, Idh3g, Pck2, Pgam2, Pgm2, Phkb, Pygm, Tpi1, Gusb and Glut4. Glut4 protein expression was also reduced and insulin-stimulated glycogen synthesis was decreased. This was associated with a reduction in the mRNA expression of Insr, Irs1 and Irs2, and the phosphorylation of Akt. These studies provide a novel role for Zip7 in glucose metabolism in skeletal muscle and highlight the importance of this transporter in contributing to glycaemic control in this tissue.

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References

Wijesekara N, Chimienti F, Wheeler M . Zinc, a regulator of islet function and glucose homeostasis. Diabetes Obes Metab. 2009; 11 Suppl 4:202-14. DOI: 10.1111/j.1463-1326.2009.01110.x. View

Huang L, Kirschke C, Lay Y, Levy L, Lamirande D, Zhang P . Znt7-null mice are more susceptible to diet-induced glucose intolerance and insulin resistance. J Biol Chem. 2012; 287(40):33883-96. PMC: 3460483. DOI: 10.1074/jbc.M111.309666. View

Hogstrand C, Kille P, Nicholson R, Taylor K . Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol Med. 2009; 15(3):101-11. DOI: 10.1016/j.molmed.2009.01.004. View

Foster M, Samman S . Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal. 2010; 13(10):1549-73. DOI: 10.1089/ars.2010.3111. View

Cousins R, Liuzzi J, Lichten L . Mammalian zinc transport, trafficking, and signals. J Biol Chem. 2006; 281(34):24085-9. DOI: 10.1074/jbc.R600011200. View

Muscat G, Wagner B, Hou J, Tangirala R, Bischoff E, Rohde P . Regulation of cholesterol homeostasis and lipid metabolism in skeletal muscle by liver X receptors. J Biol Chem. 2002; 277(43):40722-8. DOI: 10.1074/jbc.M206681200. View

Ma Y, Tao R, Liu Q, Li J, Tian J, Zhang X . PTP1B inhibitor improves both insulin resistance and lipid abnormalities in vivo and in vitro. Mol Cell Biochem. 2011; 357(1-2):65-72. DOI: 10.1007/s11010-011-0876-4. View

Shimokawa T, Kato M, Ezaki O, Hashimoto S . Transcriptional regulation of muscle-specific genes during myoblast differentiation. Biochem Biophys Res Commun. 1998; 246(1):287-92. DOI: 10.1006/bbrc.1998.8600. View

Ilouz R, Kaidanovich O, Gurwitz D, Eldar-Finkelman H . Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun. 2002; 295(1):102-6. DOI: 10.1016/s0006-291x(02)00636-8. View

10.

Taylor K, Hiscox S, Nicholson R, Hogstrand C, Kille P . Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Sci Signal. 2012; 5(210):ra11. PMC: 3428905. DOI: 10.1126/scisignal.2002585. View

11.

Liuzzi J, Cousins R . Mammalian zinc transporters. Annu Rev Nutr. 2004; 24:151-72. DOI: 10.1146/annurev.nutr.24.012003.132402. View

12.

Maret W, Jacob C, Vallee B, FISCHER E . Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc Natl Acad Sci U S A. 1999; 96(5):1936-40. PMC: 26715. DOI: 10.1073/pnas.96.5.1936. View

13.

Simon S, Taylor C . Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood). 2001; 226(1):43-51. DOI: 10.1177/153537020122600107. View

14.

Zhu C, Hu D, Liu Y, Zhang Q, Chen F, Kong X . Fabp3 inhibits proliferation and promotes apoptosis of embryonic myocardial cells. Cell Biochem Biophys. 2011; 60(3):259-66. PMC: 3112483. DOI: 10.1007/s12013-010-9148-2. View

15.

Taylor K, Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson R . ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer Cells. Endocrinology. 2008; 149(10):4912-20. DOI: 10.1210/en.2008-0351. View

16.

Bin B, Fukada T, Hosaka T, Yamasaki S, Ohashi W, Hojyo S . Biochemical characterization of human ZIP13 protein: a homo-dimerized zinc transporter involved in the spondylocheiro dysplastic Ehlers-Danlos syndrome. J Biol Chem. 2011; 286(46):40255-65. PMC: 3220551. DOI: 10.1074/jbc.M111.256784. View

17.

Wang S, Dowhan D, Eriksson N, Muscat G . CARM1/PRMT4 is necessary for the glycogen gene expression programme in skeletal muscle cells. Biochem J. 2012; 444(2):323-31. DOI: 10.1042/BJ20112033. View

18.

Delli A, Vaziri-Sani F, Lindblad B, Elding-Larsson H, Carlsson A, Forsander G . Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study. Diabetes. 2012; 61(10):2556-64. PMC: 3447907. DOI: 10.2337/db11-1659. View

19.

Ferdousi S, Mia A . Serum levels of copper and zinc in newly diagnosed type-2 diabetic subjects. Mymensingh Med J. 2012; 21(3):475-8. View

20.

Crowther L, Wang S, Eriksson N, Myers S, Murray L, Muscat G . Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells. Physiol Genomics. 2010; 43(4):213-27. DOI: 10.1152/physiolgenomics.00195.2010. View