Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Public Health and Preventive Medicine, School of Medicine, Jianghan University, Wuhan, Hubei, China.
J Nutr Biochem. 2021 Oct;96:108810. doi: 10.1016/j.jnutbio.2021.108810. Epub 2021 Jun 27.
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 rats a high-fat (45%) and sucrose 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 high-fat and sucrose-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response was activated in GDM dams, characterized by the up-regulation of glucose-regulated protein 78, phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase, and the inositol-requiring enzyme 1α. Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B 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.
妊娠期糖尿病（GDM）是最常见的妊娠并发症之一，会对孕妇及其后代产生不良后果。内质网（ER）应激与胰岛素抵抗有关，并涉及 GDM 的发生。锌、硒和铬已被证明通过多种机制维持血糖稳态，但这些微量元素如何影响 GDM 中的胰岛素抵抗和 ER 应激在很大程度上尚不清楚。为了解决这个问题，我们通过给雌性 Sprague-Dawley 大鼠喂食高脂肪（45%）和蔗糖饮食来诱导 GDM 大鼠模型，同时在交配前 6 周至哺乳期结束时单独或联合补充锌（10mg/kg.bw）、硒（20ug/kg.bw）和铬（20ug/kg.bw）。分析了母体代谢参数、肝 ER 应激和胰岛素信号。结果表明，锌、硒和铬联合补充可显著缓解高脂肪和蔗糖诱导的葡萄糖不耐受和整个实验期间的氧化应激。GDM 母鼠的肝 ER 应激和未折叠蛋白反应被激活，表现为葡萄糖调节蛋白 78、磷酸化蛋白激酶 RNA 样内质网激酶和肌醇需求酶 1α 的上调。锌、硒和铬补充可显著防止这种激活，从而促进磷酸化蛋白激酶 B 相关的胰岛素信号转导和维持血糖稳态。总之，锌、硒和铬的补充可能是通过减轻肝 ER 应激来预防 GDM 发展的一种有前途的方法。
