Zinc, Selenium and Chromium Supplementation Improves Insulin Resistance by Preventing Hepatic Endoplasmic Reticulum Stress in Diet-Induced Gestational Diabetes Rats

Abstract

Objectives 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. Methods 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. Results The results showed that zinc, selenium and chromium 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 rats, 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. Conclusions Zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress. Funding Sources This work was financially supported by the Angel Nutritech Nutrition Fund (AF2017003) and the National Natural Science Foundation of China (NSFC, 81373006 and 81973043).