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 3.0 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.

Selenoproteins: Molecular Pathways and Physiological Roles

“…In accordance with these observations, the results of several clinical trials that investigated the chemopreventive effects of dietary Se supplementation revealed that increased intake of Se above the nutrient requirements may raise the risk of type 2 diabetes mellitus in humans (222,327). Although the exact mechanism of the diabetogenic effect of high Se intake remains unclear, increased expression of GPx1, SelP, MsrB1, and SelS has been implicated in the development of type 2 diabetes and insulin resistance (198,256,287,382). At least some of these effects could be attributed to diminished intracellular H 2 O 2 levels as a result of high GPx1 activity leading to suppression of insulin signaling and increased insulin secretion, similar to GPx1-overexpressing mice (386).…”

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs

“…Whole-blood samples of individual pigs were collected at week 0 and then biweekly after overnight food deprivation (8 h) to prepare plasma samples as previously described (3). Plasma concentrations of total TGs, total cholesterol (TC), nonesterified fatty acids (NEFAs), glucose, and insulin (at weeks 6 and 11) were analyzed as previously described (9).…”

“…Alterations of these factors were associated with expressions of 12 selenoproteins (1,3,5,9,18,19). However, to the best of our knowledge, there was no information on effects of dietary selenium, in particular high selenium intake, on body protein metabolism, although protein synthesis was reported to negatively regulate insulin sensitivity (20,21) and a high protein diet inhibited the development of type 2 diabetes (22).…”

“…Although dietary selenium restriction in mice ameliorated most of the phenotypes (2), prolonged feeding of a high-selenium diet (3 mg Se/kg) caused mild gestational diabetes in pregnant rats and insulin resistance in their offspring (3). Likewise, 2 pig studies (4,5) showed the potential of high selenium intakes in causing hyperinsulinemia.…”

Supplementary Seleno-L-methionine Suppresses Active Cutaneous Anaphylaxis Reaction

“…GPx and TR are anti-oxidant enzymes and their activities are significantly increased in mice or rats fed high supplemental level of selenium containing diet compared with mice or rats fed normal level of selenium containing diet. [33][34][35] Recently, it was reported that increasing GPx and TR activities alter the immune response toward a Th1 phenotype. 36) SelS is also considered to regulate the immune response and redox balance.…”