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首页> 外文期刊>The Journal of Nutritional Biochemistry >Supranutritional selenium intake from enriched milk casein impairs hepatic insulin sensitivity via attenuated IRS/PI3K/AKT signaling and decreased PGC-1 alpha expression in male Sprague-Dawley rats
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Supranutritional selenium intake from enriched milk casein impairs hepatic insulin sensitivity via attenuated IRS/PI3K/AKT signaling and decreased PGC-1 alpha expression in male Sprague-Dawley rats

机译：来自富集的牛奶酪蛋白的Supranutritional硒摄入量通过减毒/ pi3k / akt信号传导损害肝胰岛素敏感性，并且在雄性Sprague-dawley大鼠中降低了PGC-1α表达

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Selenium (Se)-enriched milk provides antioxidant benefits and has therapeutic potential against cancer. However, both antidiabetic and prodiabetic effects have been attributed to Se. Our objective was to evaluate the effect of Se -enriched milk casein on insulin sensitivity in rats when given at the requirement of 0.25 ppm Se and supranutritionally on both low-and high-fat diets. Two hundred sixteen male Sprague-Dawley rats were fed low-or high-fat diets containing one; two or eight times the Se requirement in a randomized block design. After 7 weeks, 72 rats were subjected to the hyperinsulinemic-euglycemic clamp with [3-H-3]glucose infusion to estimate glucose fluxes. Tissues were collected from the remaining 144 rats 8 min after ip saline or insulin injection. During hyperinsulinemic-euglycemic clamps, glucose infusion rate was 22% lower (P=.058), and endogenous glucose production was 76% higher (P=.054) when Se content increased from one to eight times the requirement on low -fat diets, indicating impaired hepatic insulin sensitivity. Se also decreased the ability for insulin to stimulate Akt phosphorylation at Thr308. Hepatic oxidation state and expression of selenoprotein P and glutathione peroxidase-1 were unaffected while expression of insulin receptor substrate (IRS) -1 and-2 and PPARy coactivator-alpha (PGC-1 alpha) decreased with supranutritional Se and high -fat intake. In addition, hepatic expression of regulatory and catalytic subunits of phosphatidylinositol 3-kinase (PI3K) decreased with supranutritional intake of Se. Se intake from enriched casein up to eight times the requirement impairs hepatic insulin sensitivity in a mechanism similar to fat feeding, via attenuated IRS/PI3K/Akt signaling and decreased PGC-1 alpha expression. (C) 2017 Elsevier Inc. All rights reserved.
机译：富硒牛奶具有抗氧化作用，对癌症具有治疗潜力。然而，抗糖尿病和产生糖尿病的作用都归因于硒。我们的目的是评估富硒牛奶酪蛋白对大鼠胰岛素敏感性的影响，当在低脂肪和高脂肪饮食中给予0.25 ppm硒和超营养时。216只雄性Sprague-Dawley大鼠被喂食含有一种蛋白质的低脂肪或高脂肪饮食；在随机区组设计中是Se要求的两到八倍。7周后，72只大鼠接受高胰岛素正血糖钳夹和[3-H-3]葡萄糖输注，以估计葡萄糖流量。在注射生理盐水或胰岛素8分钟后，从其余144只大鼠收集组织。在高胰岛素-正血糖钳夹期间，当硒含量从低脂饮食所需的1倍增加到8倍时，葡萄糖输注率降低22%（P=0.058），内源性葡萄糖生成增加76%（P=0.054），表明肝脏胰岛素敏感性受损。硒还降低了胰岛素在Thr308刺激Akt磷酸化的能力。肝脏氧化状态和硒蛋白P和谷胱甘肽过氧化物酶-1的表达不受影响，而胰岛素受体底物（IRS）-1和-2以及PPARy辅激活因子α（PGC-1α）的表达随着超营养硒和高脂肪摄入而降低。此外，肝脏磷脂酰肌醇3-激酶（PI3K）调节和催化亚基的表达随着硒的超营养摄入而降低。从富含酪蛋白中摄入高达需求量八倍的硒，通过减弱IRS/PI3K/Akt信号和降低PGC-1α表达，以类似于脂肪喂养的机制损害肝脏胰岛素敏感性。（C） 2017爱思唯尔公司版权所有。

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