Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects.

Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects.
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DOI:
10.2337/db13-1396
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发表时间:
2014-03
期刊:
影响因子:
7.7
通讯作者:
Klein S
Klein S
中科院分区:
医学1区
文献类型:
--
作者:
Fabbrini E;Serafini M;Colic Baric I;Hazen SL;Klein S

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氧化应激被认为与肥胖相关的胰岛素抵抗的发病机制有关。我们评估了循环尿酸(UA)水平的变化是否会影响以下方面:1)全身(血浆和唾液)非酶抗氧化能力;2)全身(尿8-异前列腺素-F2α)和肌肉(碳化蛋白含量)氧化应激的标志物;以及3)全身胰岛素敏感性(高胰岛素-正常血糖钳夹过程中葡萄糖摄取增加的百分比)。研究对象为31例体重指数(BMI)37.1±0.7 kg/m2的肥胖者,其中高血尿酸(UA;7.1±0.4 mg/dL;n=15)和正常血尿酸(NUA;4.5±0.2 mg/dL;n=16),13例血尿酸(UA)水平通过输注重组尿酸酶降至0后再次研究。与NUA组相比,华裔受试者的NEAC增加20-90%,但胰岛素敏感性(40%)和氧化应激标志物水平(30%)更低(均P<0.05)。急性UA减少导致NEAC下降45-95%,全身和肌肉氧化应激标志物水平上升25-40%(均P<0.05),但不影响胰岛素敏感性(从168±25%到156±17%,P=NS)。这些结果表明,循环中的尿酸是一种主要的抗氧化剂,可能有助于保护机体免受自由基氧化损伤。然而,氧化应激不是体内胰岛素作用的主要决定因素。
Oxidative stress is purported to be involved in the pathogenesis of obesity-associated insulin resistance. We evaluated whether alterations in levels of circulating uric acid (UA), a systemic antioxidant, affects the following: 1) systemic (plasma and saliva) nonenzymatic antioxidant capacity (NEAC); 2) markers of systemic (urinary 8-iso-prostaglandin-F2α) and muscle (carbonylated protein content) oxidative stress; and 3) whole-body insulin sensitivity (percentage increase in glucose uptake during a hyperinsulinemic-euglycemic clamp procedure). Thirty-one obese subjects (BMI 37.1 ± 0.7 kg/m2) with either high serum UA (HUA; 7.1 ± 0.4 mg/dL; n = 15) or normal serum UA (NUA; 4.5 ± 0.2 mg/dL; n = 16) levels were studied; 13 subjects with HUA levels were studied again after reduction of serum UA levels to 0 by infusing a recombinant urate oxidase. HUA subjects had 20–90% greater NEAC, but lower insulin sensitivity (40%) and levels of markers of oxidative stress (30%) than subjects in the NUA group (all P < 0.05). Acute UA reduction caused a 45–95% decrease in NEAC and a 25–40% increase in levels of systemic and muscle markers of oxidative stress (all P < 0.05), but did not affect insulin sensitivity (from 168 ± 25% to 156 ± 17%, P = NS). These results demonstrate that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, oxidative stress is not a major determinant of insulin action in vivo.
同硫醇使用对尿酸盐浓度和心血管结局的影响。
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