The zinc transporter, Slc39a7 (Zip7) is implicated in glycaemic control in skeletal muscle cells

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 <em>Zip7</em> mRNA we have identified that <em>Zip7</em> regulates glucose metabolism in skeletal muscle cells. An siRNA targeting <em>Zip7</em> mRNA down regulated <em>Zip7</em> 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 <em>Agl</em>, <em>Dlst</em>, <em>Galm, Gbe1, Idh3g, Pck2</em>, <em>Pgam2, Pgm2, Phkb, Pygm, Tpi1, Gusb and Glut4</em>. Glut4 protein expression was also reduced and insulin-stimulated glycogen synthesis was decreased. This was associated with a reduction in the mRNA expression of <em>Insr, Irs1</em> and <em>Irs2</em>, and the phosphorylation of Akt. These studies provide a novel role for <em>Zip7</em> in glucose metabolism in skeletal muscle and highlight the importance of this transporter in contributing to glycaemic control in this tissue.