A high-selenium diet induces insulin resistance in gestating rats and their offspring

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• 作者：Min-Shu Zeng^a ; Xi Li^a ; Yan Liu^a ; Hua Zhao^a ; Ji-Chang Zhou^a ; Ke Li^a ; Jia-Qiang Huang^a ; Lv-Hui Sun^a ; Jia-Yong Tang^a ; Xin-Jie Xia^a ; ^b ; Kang-Ning Wang^a ; Xin Gen Lei^a ; ^c ; ^{XL20@cornell.edu}
• 关键词：Akt2 ; serine/threonine protein kinase 2 ; BD ; basal diet ; FPG ; fasting plasma glucose ; FPI ; fasting plasma insulin ; FoxO1 ; forkhead box O1 ; Gapdh ; glyceraldehyde-3-phosphate dehydrogenase ; GDM ; gestational diabetes mellitus ; Gpx ; glutathione peroxidase ; HO
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 April, 2012
• 卷：52
• 期：8
• 页码：1335-1342
• 文件大小：588 K

摘要

Although supranutrition of selenium (Se) is considered a promising anti-cancer strategy, recent human studies have shown an intriguing association between high body Se status and diabetic risk. This study was done to determine if a prolonged high intake of dietary Se actually induced gestational diabetes in rat dams and insulin resistance in their offspring. Forty-five 67-day-old female Wistar rats (n = 15/diet) were fed a Se-deficient (0.01 mg/kg) corn-soy basal diet (BD) or BD + Se (as Se-yeast) at 0.3 or 3.0 mg/kg from 5 weeks before breeding to day 14 postpartum. Offspring (n = 8/diet) of the 0.3 and 3.0 mg Se/kg dams were fed with the same respective diet until age 112 days. Compared with the 0.3 mg Se/kg diet, the 3.0 mg/kg diet induced hyperinsulinemia (P < 0.01), insulin resistance (P < 0.01), and glucose intolerance (P < 0.01) in the dams at late gestation and/or day 14 postpartum and in the offspring at age 112 days. These impairments concurred with decreased (P < 0.05) mRNA and/or protein levels of six insulin signal proteins in liver and muscle of dams and/or pups. Dietary Se produced dose-dependent increases in Gpx1 mRNA or GPX1 activity in pancreas, liver, and erythrocytes of dams. The 3.0 mg Se/kg diet decreased Selh (P < 0.01), Sepp1 (P = 0.06), and Sepw1 (P < 0.01), but increased Sels (P < 0.05) mRNA levels in the liver of the offspring, compared with the 0.3 mg Se/kg diet. In conclusion, supranutrition of Se as a Se-enriched yeast in rats induced gestational diabetes and insulin resistance. Expression of six selenoprotein genes, in particular Gpx1, was linked to this metabolic disorder.