Role of Supplementary Selenium on the Induction of Insulin Resistance and Oxidative Stress in NSY Mice Fed a High Fat Diet
Role of Supplementary Selenium on the Induction of Insulin Resistance and Oxidative Stress in NSY Mice Fed a High Fat Diet
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DOI：
10.1248/bpb.b17-00622
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发表时间：
2018-01-01
影响因子：
2
通讯作者：
Ueno, Hitoshi
中科院分区：
文献类型：
--
作者：
Murano, Koichi;Ogino, Hirofumi;Ueno, Hitoshi
在高脂饮食（HFD）和给予含硒-L-蛋氨酸（SeMet）的水12周的NSY小鼠中研究了补充硒对糖尿病小鼠模型中胰岛素抵抗和氧化应激的诱导作用。在HFD小鼠中观察到口服葡萄糖耐量试验（OGTT）、胰岛素耐量试验和非空腹血糖水平的显著增加，以及OGTT和非空腹血浆胰岛素水平的显著增加。HFD小鼠血浆脂联素水平降低，游离脂肪酸（FFA）水平升高。补充SeMet显著增加了HFD小鼠的OGTT血糖水平和正常饮食小鼠的血浆FFA水平。测定了6种硒蛋白的mRNA水平，并选择谷胱甘肽过氧化物酶（GPx）1和硒蛋白P（SelP）作为可能与肝脏中的胰岛素抵抗或氧化应激相关的候选物。在HFD和SeMet补充的小鼠中肝脏GPx 1表达升高，并且在HFD的小鼠中SelP表达增加。肝组织的组织学观察显示，HFD小鼠的实质细胞肥大，4-羟基-2-壬烯醛显著表达，表明脂质蓄积和氧化应激诱导。肝蛋白酪氨酸磷酸酶活性也增加了HFD。这些结果表明，在NSY小鼠的HFD肝脂质积累促进氧化应激和肝SelP的表达，和补充SeMet诱导肝GPx 1的表达。
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.