Effects of dietary Se deficiency on the metabolic phenotype and glucose metabolism‐related gene expression of the diet‐restricted GPX1 overexpressing mice

Abstract

We previously reported that diet‐restriction rescued all the type 2 diabetes‐like phenotypes except for hyperinsulinemia in mice overexpressing the Se‐dependent glutathione peroxidase 1 (OE). This study was to determine effects of dietary Se deficiency on the metabolic phenotypes and related gene expression in pancreatic islets of the diet‐restricted OE mice over their wild‐type (WT) mice. Forty‐seven individually reared male OE and WT mice were fed Se‐adequate (0.4 mg Se/kg) or Se‐deficient (< 0.02 mg Se/kg) diet at 2 g/d starting at 4 wk of age for 2 wk, 2.5 g/d for the second 2 wk, and 3 g/d for another 8 wk. Dietary Se deficiency equalized the lower body weight of the Se‐adequate OE mice to that of the WT mice, but showed no significant effect on fasting plasma glucose concentration, body insulin or glucose tolerance or the glucose‐stimulated insulin secretion in either genotype. While the genotype effect (P < 0.05) was seen on islet mRNA levels of pdx1, beta2, p53, and glut2, dietary Se deficiency up‐regulated (P < 0.05) those of gk1, ins1, pdx1, preglucagon, and ucp2. There was a strong genotype and dietary Se interaction on islet mRNA levels of beta2, p53 and glut2. In conclusion, dietary Se deficiency affected the body weights and the islet mRNA expression of glucose metabolism‐related genes in the diet‐restricted OE and WT mice, but did not remove their genotype difference in hyperinsulinemia (NIH DK 53018).