Effect of high dietary Se intake and GPX1 overproduction on mouse susceptibility to gestational diabetes

Abstract

We previously reported type 2 diabetes‐like phenotypes in glutathione peroxidase‐1 (GPX1)‐overexpressing mice (OE) and gestational diabetes in rats fed a high‐Se (3 mg/kg) diet. This study was to determine if these 2 factors induced and/or exacerbated gestational diabetes in mice. An experiment was conducted with 3 genotypes of mice: OE, GPX1−/−, and wild‐type (WT) (2–6 mo, females, n = 12 per genotype by treatment) and 2 levels of dietary Se: 0.4 or 1.0 mg Se/kg (as sodium selenite in a Torula‐yeast based diet) from 3 wk before breeding to d 21 postpartum. Genotypes affected (P < 0.05) body weight, blood glucose, plasma insulin, and glucose and insulin tolerances at all 4 tested time‐points. While the OE mice had elevated (P < 0.05) body weight, blood glucose and plasma insulin compared with the WT and GPX1−/− mice, they showed better glucose tolerance throughout and improved insulin sensitivity on d 19 of gestation. The high Se diet was hyperinsulinemic and hypoglycemic (P < 0.05) and impaired insulin and glucose tolerances in the WT and OE mice on d 19 of gestation and/or d 10 postpartum. The high Se diet also decreased expression of insulin synthesis and signaling‐related genes and proteins in islets, liver, and muscle of the WT and OE mice. In conclusion, although high dietary Se intake did not induce overt gestational diabetes in the OE mice, knockout of GPX1 constrained adverse effects of high Se in this regard(NIH DK53018).