Translational Research Center of Nutrition and Ageing, Scientific and Technological Pole, Italian National Institute of Health and Science on Aging (INRCA), Ancona, Italy.
Pediatric Research Institute at the Department of Pediatrics, Wendy L. Novak Diabetes Care Center, University of Louisville, Louisville, KY, USA.
Biofactors. 2017 Nov;43(6):770-784. doi: 10.1002/biof.1386. Epub 2017 Aug 27.
Impaired zinc homeostasis is observed in diabetes mellitus (DM2) and its complications. Zinc has a specific role in pancreatic β-cells via insulin synthesis, storage, and secretion. Intracellular zinc homeostasis is tightly controlled by zinc transporters (ZnT and Zip families) and metallothioneins (MT) which modulate the uptake, storage, and distribution of zinc. Several investigations in animal models demonstrate the protective role of MT in DM2 and its cardiovascular or renal complications, while a copious literature shows that a common polymorphism (R325W) in ZnT8, which affects the protein's zinc transport activity, is associated with increased DM2 risk. Emerging studies highlight a role of other zinc transporters in β-cell function, suggesting that targeting them could make a possible contribution in managing the hyperglycemia in diabetic patients. This article summarizes the current findings concerning the role of zinc homeostasis in DM2 pathogenesis and development of diabetic cardiomyopathy and nephropathy and suggests novel therapeutic targets. © 2017 BioFactors, 43(6):770-784, 2017.
锌稳态失调在 2 型糖尿病（DM2）及其并发症中较为常见。锌通过胰岛素的合成、储存和分泌在胰岛β细胞中具有特殊作用。细胞内锌稳态由锌转运体（ZnT 和 Zip 家族）和金属硫蛋白（MT）严格控制，调节锌的摄取、储存和分布。在动物模型中的几项研究表明 MT 在 DM2 及其心血管或肾脏并发症中的保护作用，而大量文献表明 ZnT8 中的一种常见多态性（R325W）影响蛋白的锌转运活性，与增加 DM2 风险有关。新的研究强调了其他锌转运体在β细胞功能中的作用，提示针对这些转运体可能有助于控制糖尿病患者的高血糖。本文总结了目前关于锌稳态在 DM2 发病机制、糖尿病性心肌病和肾病发展中的作用的研究结果，并提出了新的治疗靶点。©2017 BioFactors, 43(6):770-784, 2017.
