Maier Michelle C, Nankervis Scott, Wallace Morgan E, Develyn Tamekha, Myers Mark A
Health Innovation and Transformation Centre, Federation University Australia, Mt Helen, Victoria, Australia.
Biomedical Science, Institute of Innovation, Science and Sustainability, Federation University Australia, Mt Helen, Victoria, Australia.
J Cell Biochem. 2023 Mar;124(3):409-420. doi: 10.1002/jcb.30376. Epub 2023 Jan 30.
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 homeostasis remains unclear. In this study, the effect of the glucocorticoid dexamethasone (DEX) on insulin and Zn 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 was higher after DEX treatment, and in both C2C12 and 3T3-L1 adipocytes, free unbound Zn was increased. Insulin treatment led to a gradual increase in free Zn 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 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.
骨骼肌萎缩与循环糖皮质激素水平升高和胰岛素抵抗有关。锌在萎缩肌肉中蓄积，但萎缩、胰岛素抵抗与锌稳态之间的关系仍不清楚。在本研究中，探讨了糖皮质激素地塞米松（DEX）对胰岛素和锌稳态的影响。用DEX处理分化的C2C12骨骼肌细胞和3T3-L1脂肪细胞，显著增加了金属结合蛋白Mt1和2的mRNA表达，并改变了能量储存，如3T3-L1细胞中脂滴大小增加所示。在C2C12细胞中，DEX处理后细胞内总锌含量更高，在C2C12细胞和3T3-L1脂肪细胞中，游离未结合锌均增加。胰岛素处理导致C2C12细胞中游离锌逐渐增加，而在DEX处理的细胞中无显著变化，因此在胰岛素处理10分钟后浓度相似。这些数据表明，DEX扰乱了肌肉和脂肪细胞中的锌稳态。有必要进一步研究相关分子途径，以确定治疗骨骼肌萎缩的新治疗靶点。
