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

PLoS One. 2013 Nov 12;8(11):e79316. doi: 10.1371/journal.pone.0079316. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins / deficiency
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cell Line
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Glucose / metabolism*
  • Glycogen / metabolism
  • Insulin Resistance
  • Mice
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism*
  • Phosphorylation
  • Quadriceps Muscle / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics

Substances

  • Cation Transport Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Zip7 protein, mouse
  • Glycogen
  • Glucose

Grants and funding

This study was funded by a School of Health Sciences Seeding Grant, University of Ballarat, Victoria Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.