Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
J Trace Elem Med Biol. 2018 Mar;46:117-127. doi: 10.1016/j.jtemb.2017.12.005. Epub 2017 Dec 22.
Zinc is one of the essential trace elements and participates in numerous physiological processes. Abnormalities in zinc homeostasis often result in the pathogenesis of various chronic metabolic disorders, such as diabetes and its complications. Zinc has insulin-mimetic and anti-diabetic effects and deficiency has been shown to aggravate diabetes-induced oxidative stress and tissue injury in diabetic rodent models and human subjects with diabetes. Akt signaling pathway plays a central role in insulin-stimulated glucose metabolism and cell survival. Anti-diabetic effects of zinc are largely dependent on the activation of Akt signaling. Zn is also an inducer of metallothionein that plays important role in anti-oxidative stress and damage. However, the exact molecular mechanisms underlying zinc-induced activation of Akt signaling pathway remains to be elucidated. This review summarizes the recent advances in deciphering the possible mechanisms of zinc on Akt-mediated insulin and cell survival signaling pathways in diabetes conditions. Insights into the effects of zinc on epigenetic regulation and autophagy in diabetic nephropathy are also discussed in the latter part of this review.
锌是必需微量元素之一，参与众多生理过程。锌稳态异常常导致各种慢性代谢紊乱的发病，如糖尿病及其并发症。锌具有胰岛素模拟和抗糖尿病作用，并且已经表明在糖尿病啮齿动物模型和糖尿病患者中，缺锌会加重糖尿病引起的氧化应激和组织损伤。Akt 信号通路在胰岛素刺激的葡萄糖代谢和细胞存活中起核心作用。锌的抗糖尿病作用在很大程度上依赖于 Akt 信号的激活。Zn 也是金属硫蛋白的诱导剂，在抗氧化应激和损伤中发挥重要作用。然而，锌诱导 Akt 信号通路激活的确切分子机制仍有待阐明。本综述总结了近年来在破译锌在糖尿病情况下对 Akt 介导的胰岛素和细胞存活信号通路的可能作用机制方面的进展。本文还讨论了锌对糖尿病肾病中表观遗传调控和自噬的影响。
