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

Abstract

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 3.0mg/kg from 5 weeks before breeding to day 14 postpartum. Offspring (n=8/diet) of the 0.3 and 3.0mg Se/kg dams were fed with the same respective diet until age 112 days. Compared with the 0.3mg Se/kg diet, the 3.0mg/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 3.0mg 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 0.3mg 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.

Fig. 1

Effects of dietary Se concentration on (A) body weight (BW), (B) fasting plasma glucose concentration (FPG), (C) fasting plasma insulin concentration (FPI), and (D) HOMA-IR of dams on days 0 and 19 of gestation (D0ges and D19ges, respectively) and day 14 postpartum (D14pp). Values are means±SE, n=7 to 10. Means that do not share the same superscript letter (a, b) are different (P<0.05).

Fig. 2

Effects of dietary Se concentration on (A and B) glucose tolerance test and (C and D) insulin tolerance test in dams on days 0 (A and C) and 19 (B and D) of gestation. Values are means±SE, n=6. *P<0.05; **P<0.01, compared with the BD and 0.3 mg Se/kg groups.

Fig. 3

Effects of dietary Se concentration on (A) body weight (BW), (B) fasting plasma glucose concentration (FPG), (C) fasting plasma insulin concentration (FPI), and (D) HOMA-IR of offspring at age 112 days. Values are means±SE, n=8. Means showing different superscript letters (a, b) are different (P<0.05).

Fig. 4

Effects of dietary Se concentration on (A) glucose tolerance test and (B) insulin tolerance test of offspring at age 112 days. Values are means±SE, n=8, **P<0.01, compared with the 0.3 mg Se/kg group.

Fig. 5

Effects of dietary Se concentration on GPX activity (A) in erythrocytes of dams on day 19 of gestation and (B) in liver of dams on day 14 postpartum. Values are means±SE, n=5. Means showing different superscript letter are different (P<0.05).

Fig. 6

Effects of dietary Se concentration on relative amounts of (A) IR and (B) AKT and (C) GPX activity in liver of offspring at age 112 days. Values are means±SE, n=3 (A and B) or 6 (C). Means showing different superscript letter are different (P<0.05).