Effect of Plasma Uric Acid on Antioxidant Capacity, Oxidative Stress, and Insulin Sensitivity in Obese Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 63; no. 3; pp. 976 - 981
• Main Authors: Fabbrini, Elisa, Serafini, Mauro, Colic Baric, Irena, Hazen, Stanley L., Klein, Samuel
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2014
• Subjects: Antioxidants; Antioxidants - metabolism; Biochemistry; Biological and medical sciences; Biomarkers; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Health aspects; Humans; Insulin Resistance; Male; Medical research; Medical sciences; Medicine, Experimental; Metabolic diseases; Middle Aged; Obesity; Obesity - metabolism; Obesity Studies; Overweight persons; Oxidative Stress; Pathogenesis; Physiological aspects; Uric acid; Uric Acid - blood; Endocrinopathy; Human; Obesity; Oxidative stress; Pancreatic hormone; Sensitivity; Diabetes mellitus; Nutrition disorder; Uric acid; Antioxidant; Insulin; Nutritional status
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db13-1396

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.