title: Dietary selenium deficiency partially rescues type 2 diabetes-like phenotypes of glutathione peroxidase-1-overexpressing male mice.
abstract: This study was conducted to determine whether dietary Se deficiency precluded overproduction of glutathione peroxidase-1 (GPX1) activity in mice overexpressing (OE) this gene and thus rescued their type 2 diabetes-like phenotypes. A total of 20 male OE and wild-type (WT) mice were fed an Se-deficient (<0.02 mg/kg) diet or an Se-supplemented (0.3 mg/kg as sodium selenite) diet from 1 to 5 mo of age. Dietary Se deficiency eliminated or attenuated (P < 0.05) genotype differences in concentrations of blood glucose, plasma insulin, and/or hepatic lipids, insulin sensitivity, and glucose-stimulated insulin secretion at the end of the study. Dietary Se deficiency decreased (P < 0.05) OE islet mRNA levels of 2 key transcriptional activators (Beta2 and Foxa2) and removed genotype differences in islet mRNA levels of 7 genes (Beta2, Cfos, Foxa2, Pregluc, Ins1, p53, and Sur1) related to insulin synthesis and secretion. Compared with those of the Se-adequate OE mice, the Se-deficient OE mice had lower (P < 0.05) hepatic mRNA levels of 2 key rate-limiting enzymes for lipogenesis (Acc1) and glycolysis (Gk1), along with lower (P < 0.05) activities of hepatic glucokinase and muscle phosphoenolpyruvate carboxykinase. Dietary Se deficiency also decreased (P < 0.05) blood glucose and hepatic lipid concentrations in the WT mice. In conclusion, dietary Se deficiency precluded the overproduction of GPX1 in full-fed OE mice and partially rescued their metabolic syndromes. This alleviation resulted from modulating the expression and/or function of proinsulin genes, lipogenesis rate-limiting enzyme genes, and key glycolysis and gluconeogenesis enzymes in islets, liver, and muscle.
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Yan
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Pepper
authors.forename: Marko Z
authors.initials: MZ
authors.lastname: Vatamaniuk
authors.forename: Carol A
authors.initials: CA
authors.lastname: Roneker
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xin Gen
authors.initials: XG
authors.lastname: Lei
mesh_terms: D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet / Q000662:veterinary; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D012643:Selenium / Q000172:deficiency*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse