Dexamethasone leads to Zn 2+ accumulation and increased unbound Zn 2+ in C2C12 muscle and 3T3-L1 adipose cells.

Skeletal muscle atrophy is associated with increases in circulating glucocorticoid levels and insulin resistance. Zinc accumulates in atrophic muscle, but the relationship between atrophy, insulin resistance, and Zn 2+ homeostasis remains unclear. In this study, the effect of the glucocorticoid dexamethasone (DEX) on insulin and Zn 2+ homeostasis was explored. Treatment of differentiated C2C12 skeletal myotubes and 3T3-L1 adipocytes with DEX significantly increased mRNA expression of the metal-binding proteins Mt1 and 2 and altered energy storage as shown by the increased size of lipid droplets in 3T3-L1 cells. In C2C12 cells the total cellular Zn 2+ was higher after DEX treatment, and in both C2C12 and 3T3-L1 adipocytes, free unbound Zn 2+ was increased. Insulin treatment led to a gradual increase in free Zn 2+ in C2C12 cells, and no significant change in DEX-treated cells such that concentrations were similar 10 min after insulin treatment. These data demonstrate that DEX disturbs Zn 2+ homeostasis in muscle and fat cells. Further study of the molecular pathways involved to identify novel therapeutic targets for treatment of skeletal muscle atrophy is warranted.