engleski

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

Oxidative stress is purported to be involved in the pathogenesis of obesity-associated insulin resistance. We evaluated whether alterations in circulating uric acid (UA), a systemic antioxidant, affects: 1) systemic (plasma and saliva) non-enzimatic 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 (% 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) were studied ; 13 subjects with HUA were studied again after reduction of serum UA to 0 by infusing a recombinant urate oxidase. HUA subjects had 20-90% greater NEAC, but lower insulin sensitivity (40%) and 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 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.

Antioxidants ; Insulin Resistance ; Obesity ; Oxidative Stress ; Uric Acid

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