Norouzi Shaghayegh, Adulcikas John, Sohal Sukhwinder Singh, Myers Stephen
College of Health and Medicine, School of Health Sciences, University of Tasmania, Newnham Campus, Launceston, Tasmania, Australia.
PLoS One. 2018 Jan 26;13(1):e0191727. doi: 10.1371/journal.pone.0191727. eCollection 2018.
Zinc is a metal ion that is an essential cell signaling molecule. Highlighting this, zinc is an insulin mimetic, activating cellular pathways that regulate cellular homeostasis and physiological responses. Previous studies have linked dysfunctional zinc signaling with several disease states including cancer, obesity, cardiovascular disease and type 2 diabetes. The present study evaluated the insulin-like effects of zinc on cell signaling molecules including tyrosine, PRSA40, Akt, ERK1/2, SHP-2, GSK-3β and p38, and glucose oxidation in human and mouse skeletal muscle cells. Insulin and zinc independently led to the phosphorylation of these proteins over a 60-minute time course in both mouse and human skeletal muscle cells. Similarly, utilizing a protein array we identified that zinc could active the phosphorylation of p38, ERK1/2 and GSK-3B in human and ERK1/2 and GSK-3B in mouse skeletal muscle cells. Glucose oxidation assays were performed on skeletal muscle cells treated with insulin, zinc, or a combination of both and resulted in a significant induction of glucose consumption in mouse (p<0.01) and human (p<0.05) skeletal muscle cells when treated with zinc alone. Insulin, as expected, increased glucose oxidation in mouse (p<0.001) and human (0.001) skeletal muscle cells, however the combination of zinc and insulin did not augment glucose consumption in these cells. Zinc acts as an insulin mimetic, activating key molecules implicated in cell signaling to maintain glucose homeostasis in mouse and human skeletal muscle cells. Zinc is an important metal ion implicated in several biological processes. The role of zinc as an insulin memetic in activating key signaling molecules involved in glucose homeostasis could provide opportunities to utilize this ion therapeutically in treating disorders associated with dysfunctional zinc signaling.
锌是一种金属离子，是一种重要的细胞信号分子。值得注意的是，锌具有胰岛素模拟作用，可激活调节细胞内稳态和生理反应的细胞通路。先前的研究已将功能失调的锌信号传导与多种疾病状态联系起来，包括癌症、肥胖症、心血管疾病和2型糖尿病。本研究评估了锌对细胞信号分子（包括酪氨酸、PRSA40、Akt、ERK1/2、SHP-2、GSK-3β和p38）的胰岛素样作用，以及对人和小鼠骨骼肌细胞中葡萄糖氧化的影响。在人和小鼠骨骼肌细胞中，胰岛素和锌在60分钟的时间进程中分别导致这些蛋白质的磷酸化。同样，利用蛋白质阵列，我们发现锌可激活人骨骼肌细胞中p38、ERK1/2和GSK-3B以及小鼠骨骼肌细胞中ERK1/2和GSK-3B的磷酸化。在用胰岛素、锌或两者组合处理的骨骼肌细胞上进行葡萄糖氧化测定，结果显示单独用锌处理时，小鼠（p<0.01）和人（p<0.05）骨骼肌细胞中的葡萄糖消耗显著增加。正如预期的那样，胰岛素增加了小鼠（p<0.001）和人（p<0.001）骨骼肌细胞中的葡萄糖氧化，然而锌和胰岛素的组合并未增加这些细胞中的葡萄糖消耗。锌具有胰岛素模拟作用，可激活参与细胞信号传导的关键分子，以维持人和小鼠骨骼肌细胞中的葡萄糖稳态。锌是一种参与多种生物学过程的重要金属离子。锌作为胰岛素模拟物在激活参与葡萄糖稳态的关键信号分子方面的作用，可能为在治疗与锌信号传导功能失调相关的疾病中利用这种离子提供治疗机会。
