Department of Pediatrics, Pediatrics Research Institute, University of Louisville, Louisville, Kentucky, USA.
Hanyang University, College of Medicine and Engineering, Seoul, South Korea.
J Diabetes. 2018 Mar;10(3):213-231. doi: 10.1111/1753-0407.12620. Epub 2018 Jan 5.
Reactive oxygen and nitrogen species (ROS and RNS, respectively) are byproducts of cellular physiological processes of the metabolism of intermediary nutrients. Although physiological defense mechanisms readily convert these species into water or urea, an improper balance between their production and removal leads to oxidative stress (OS), which is harmful to cellular components. This OS may result in uncontrolled growth or, ultimately, cell death. In addition, ROS and RNS are closely related to the development of diabetes and its complications. Therefore, numerous researchers have proposed the development of strategies for the removal of ROS/RNS to prevent or treat diabetes and its complications. Some molecules that are synthesized in the body or obtained from food participate in the removal and neutralization of ROS and RNS. Metallothionein, a cysteine-rich protein, is a metal-binding protein that has a wide range of functions in cellular homeostasis and immunity. Metallothionein can be induced by a variety of conditions, including zinc supplementation, and plays a crucial role in mediating anti-OS, anti-apoptotic, detoxification, and anti-inflammatory effects. Metallothionein can modulate various stress-induced signaling pathways (mitogen-activated protein kinase, Wnt, nuclear factor-κB, phosphatidylinositol 3-kinase, sirtuin 1/AMP-activated protein kinase and fibroblast growth factor 21) to alleviate diabetes and diabetic complications. However, a deeper understanding of the functional, biochemical, and molecular characteristics of metallothionein is needed to bring about new opportunities for OS therapy. This review focuses on newly proposed functions of a metallothionein and their implications relevant to diabetes and its complications.
活性氧和氮物种（ROS 和 RNS，分别）是细胞中间营养物质代谢生理过程的副产物。虽然生理防御机制可以将这些物质轻易地转化为水或尿素，但它们的产生和清除之间的不平衡会导致氧化应激（OS），对细胞成分造成损害。这种 OS 可能导致不受控制的生长，或者最终导致细胞死亡。此外，ROS 和 RNS 与糖尿病及其并发症的发展密切相关。因此，许多研究人员提出了清除 ROS/RNS 的策略，以预防或治疗糖尿病及其并发症。一些在体内合成或从食物中获得的分子参与了 ROS 和 RNS 的清除和中和。金属硫蛋白是一种富含半胱氨酸的蛋白质，是一种金属结合蛋白，在细胞内稳态和免疫中具有广泛的功能。金属硫蛋白可以被多种条件诱导，包括锌补充，在介导抗 OS、抗凋亡、解毒和抗炎作用方面起着至关重要的作用。金属硫蛋白可以调节各种应激诱导的信号通路（丝裂原激活蛋白激酶、Wnt、核因子-κB、磷酸肌醇 3-激酶、Sirtuin 1/AMP 激活蛋白激酶和成纤维细胞生长因子 21），以减轻糖尿病和糖尿病并发症。然而，需要更深入地了解金属硫蛋白的功能、生化和分子特性，才能为 OS 治疗带来新的机会。本综述重点介绍了金属硫蛋白的新提出的功能及其与糖尿病及其并发症的相关性。
