Role of Supplementary Selenium on the Induction of Insulin Resistance and Oxidative Stress in NSY Mice Fed a High Fat Diet

• Published in: Biological & pharmaceutical bulletin 2018/01/01, Vol.41(1), pp.92-98
• Main Authors: Murano, Koichi, Ogino, Hirofumi, Okuno, Tomofumi, Arakawa, Tomohiro, Ueno, Hitoshi
• Format: Article
• Language: English
• Subjects: Accumulation; Adiponectin; Animals; Biomarkers - blood; Blood glucose; Blood Glucose - analysis; diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diet, High-Fat - adverse effects; Dietary Supplements; Fasting; Glucose; Glucose tolerance; Glutathione peroxidase; glutathione peroxidase 1; High fat diet; Hypertrophy; Insulin; Insulin Resistance; Laboratory testing; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Methionine; Mice; Mice, Inbred Strains; mRNA; Oxidation resistance; Oxidative stress; Oxidative Stress - drug effects; Protein-tyrosine-phosphatase; Selenium; Selenium - metabolism; Selenomethionine - pharmacology; selenoprotein P; Selenoproteins; Selenoproteins - biosynthesis
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00622

The role of supplementary selenium on the induction of insulin resistance and oxidative stress in a diabetic mouse model was investigated in NSY mice on a high fat diet (HFD) and administered seleno-L-methionine (SeMet)-containing water for 12 weeks. Significant increases in oral glucose tolerance-tested (OGTT), insulin tolerance-tested, and non-fasting blood glucose levels were observed in mice on a HFD, as well as the significant increases in OGTT and non-fasting plasma insulin levels. Mice on a HFD had decreased plasma adiponectin levels and increased free fatty acid (FFA) levels. Supplementary SeMet significantly augmented OGTT blood glucose levels in mice on a HFD and plasma FFA levels in mice on a normal diet. The mRNA levels of six selenoproteins were measured, and glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were selected as candidates that may be associated with insulin resistance or oxidative stress in the liver. Hepatic GPx1 expression was elevated in mice on a HFD and SeMet supplementation, and SelP expression increased in mice on a HFD. Histopathological observations in hepatic tissues showed hypertrophy of parenchymal cells and significant expression of 4-hydroxy-2-nonenal in mice on a HFD, indicating lipid accumulation and oxidative stress induction. Hepatic protein tyrosine phosphatase activity also increased by a HFD. These results suggest that hepatic lipid accumulation in NSY mice on a HFD promoted oxidative stress and hepatic SelP expression, and supplementary SeMet induced hepatic GPx1 expression.