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.
- Received September 9, 2013.
- Accepted December 4, 2013.
- © 2013 by the American Diabetes Association.
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