Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. To address this, a GDM rat model was induced by feeding female Sprague-Dawley (SD) rats a high-fat (45%) and sucrose (HFS) diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. The results showed that zinc, selenium and chromium co-supplementation dramatically alleviated HFS-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response (UPR) was activated in GDM dams, characterized by the up-regulation of glucose-regulated protein 78 (GRP78), phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), and the inositol-requiring enzyme 1α (p-IRE1α). Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B (p-AKT) related insulin signaling and maintenance of glucose homeostasis. In conclusion, zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress.

妊娠糖尿病（GDM）是最常见的妊娠并发症之一，会给孕妇及其后代带来不良后果。内质网 (ER) 应激与胰岛素抵抗相关，并与 GDM 的发生有关。锌、硒和铬已被证明可以通过多种机制维持葡萄糖稳态，但这些微量元素如何影响 GDM 中的胰岛素抵抗和 ER 应激尚不清楚。为了解决这个问题，通过给雌性 Sprague-Dawley (SD) 大鼠喂食高脂肪 (45%) 和蔗糖 (HFS) 饮食，同时添加锌 (10 mg/kg.bw)、硒 (20 ug) 来诱导 GDM 大鼠模型。从交配前6周到哺乳期结束，每天单独或联合补充铬（20ug/kg.bw）。分析了母体代谢参数、肝脏 ER 应激和胰岛素信号传导。结果表明，在整个实验期间，锌、硒和铬的共同补充显着减轻了 HFS 诱导的葡萄糖不耐受和氧化应激。 GDM 母鼠的肝脏 ER 应激和未折叠蛋白反应 (UPR) 被激活，其特征是葡萄糖调节蛋白 78 (GRP78) 上调，磷酸化蛋白激酶 RNA 样内质网激酶 (p-PERK) ，以及肌醇需求酶 1α (p-IRE1α)。补充锌、硒和铬可显着阻止这种激活，从而有助于促进磷酸化蛋白激酶 B (p-AKT) 相关的胰岛素信号传导和葡萄糖稳态的维持。总之，补充锌、硒和铬可能是通过减轻肝脏 ER 应激来预防 GDM 发展的一种有前景的方法。