The Effect Of Dietary Selenium On Insulin Resistance And Selenoprotein Expressions In The Mother Rats And Their Offspring

In this study we investigated the influence of dietary selenium excess or deficiency on glucose metabolism of mother rats and their offspring, also the relationship between differential expression selenoprotein genes and insulin regulated genes were investigated in order to implore the mechanism of gestational diabetes.In the first experiment, after1wk’s adaptation with Se-deficient basal diet (BD),45healthy Wistar female rats were randomly divided into3groups (15replicates in each treatment and1rat in each replicate) fed with BD and BD supplemented with0.3(BD+0.3mg Se/kg) and3.0mg Se/kg (BD+3.0mg Se/kg) in Se-rich yeast respectively for5wks. The basic diets were the same in all groups and based on corn-soybean. Then the rats were mated for pregnancy and fed with the diets until killed for fresh plasma and tissue sampling at the end of the2nd wk after they gave birth. Erythrocytes samples were also periodically collected during the pregnancy. Measured physiological and biochemical indexes, and detection of selenoprotein and insulin-related gene expression by real-time quantitative PCR (RT-qPCR). Results of first experiment:There were no difference of total cholesterol (TC)(P>0.05), but had increasing triglyceride (TG), especially BD group (P<0.05) with rising level of dietary Se. In the liver of the postpartum mother:the gene expressions of Akt2, Insr, Irsl were down-regulated (P<0.04to0.09) with the increasing level of dietary Se; but the gene expressions of Irs2highest in BD and lowest in BD+3.0groups (P<0.05); the gene expressions of Gpxl, Selh, Sepwl were significantly lowest in BD than other two groups (P<0.05). In the muscle of the postpartum mother:the gene expressions of Akt2was up-regulated (P<0.05) with the increasing level of dietary Se; and the gene expressions of Selh, Sels, Sepwl were significantly lowest in BD than other two groups (P<0.05). The GPX activity strikingly increasing in19d red blood cells of gestation and14d postpartum maternal liver with rising level of dietary Se (P<0.05).In the second experiment, the offspring of the mother rats in BD+0.3mg Se/kg and BD+3.0mg Se/kg groups (8replicates in each treatment (female vs. male=4:4) and1rat in each replicate) were fed with the same diets as those of their mothers, did ipGTT and ITT in110d, then killed at16-wk old to collect samples. The body weights (BW) of all the animals were measured weekly. Measured physiological and biochemical indexes, and detection of selenoprotein and insulin-related gene expression by real-time quantitative PCR (RT-qPCR). Results of second experiment: The BWs of the offspring in the BD+3.0group were significantly higher at4-7-wk (P<0.01) and8wk (P<0.05) than BD+0.3group. At the112d, the TC and TG have no difference between the two groups (P>0.05), but the FPI and HOMA-IR in BD+3.0group were significantly higher (P<0.05) than those in the BD+0.3group. In the110d BD+3.0group, blood glucose at15min and30min in glucose tolerant test (ipGTT) and at30min and60min in insulin tolerant test (ITT) were strikingly higher (P<0.01) than those in the BD+0.3group. In the liver of112d offspring:the gene expressions of Akt2, Insr, Irsl were significantly down-regulated (P<0.01), also downregulation of hepatic IR and AKT protein levels, and36%decrease (P=0.06) in the mRNA level of FoxO1. high-Se diet significantly down-regulated the gene expressions of Selh (P<0.01), Sepw1(P<0.05), but significantly up-regulated the gene expressions of Sels in BD+3.0group (P <0.05). Hepatic Sepp1mRNA was also decreased (18%, P=0.06) by the high-Se diet. In the muscle of112d offspring:the gene expressions of Irs2and Pgc-1were down-regulated in BD+3.0group (P<0.01). The GPX activity strikingly higher in red blood cells and liver of BD+3.0than BD+0.3group offspring (P<0.05).In conclusion, the dietary high-Se induced insulin resistance of gestational and postpartum mother rats and caused the overweight of offspring before adulthood. Under the effect of the maternal high Se status and dietary high-Se intake, the adult offspring appeared insulin resistance and glucose impairment. The dietary high-Se induced differnent expressions of mRNA of some insulin signal proteins and/or selenoproteins (Gpxl, Selh, Sels, Seppl, Sepw1) in liver and muscle of mather rats and their offspring. The selenoproteins, especially GPX1, were associated with insulin resistance. Although the expressions of some insulin signaling related genes and selenoprotein genes were influenced by dietary Se deficiency, there was no insulin resistance appeared in mother rats.