title: Xanthine oxidoreductase activity is correlated with insulin resistance and subclinical inflammation in young humans.
abstract: The enzyme xanthine oxidoreductase (XOR) catalyzes the formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are products of purine metabolism starting from ribose-5-phosphate. Besides the synthesis of UA, basic research has suggested that XOR is involved in the regulation of reactive oxygen species, adipogenesis, and peroxisome proliferator-activated receptor-γ (PPAR-γ). XOR activity has shown to be much lower in humans than in rodents, which makes its accurate measurement difficult. Recently, a novel human plasma XOR activity assay has been established using a combination of liquid chromatography (LC) and triple quadrupole mass spectrometry (TQMS) to detect [13C2,15N2]UA using [13C2,15N2]xanthine as a substrate. Using this novel assay, we for the first time determine plasma XOR activity in humans, and evaluate its association with insulin resistance, high-sensitivity C-reactive protein (hsCRP) levels, and other parameters.
  
  
  
  Of the 29 volunteers who wished to participate in the study, 3 were excluded; of the remaining, 11 were female and 15 were male with a mean age of 25.9±3.3years. Blood samples were collected under fasting conditions in the early morning to measure XOR activity and other parameters.
  
  
  
  The natural logarithmic value of XOR activity (ln-XOR) in plasma was 3.4±0.8pmol/h/mL. Ln-XOR had a positive correlation with UA and body mass index (BMI) and a negative correlation with quantitative insulin sensitivity check index (QUICKI) and adiponectin. In addition, ln-XOR had a positive correlation with hsCRP levels, which serves as a marker of chronic inflammation.
  
  
  
  The present study has shown that XOR activity is correlated with serum UA levels in humans. Furthermore, even in young subjects, XOR activity is correlated with insulin resistance, BMI, and subclinical inflammation. Thus, XOR activity may be potentially involved in adiposity and subclinical inflammation in humans.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Kahori Watanabe
authors.initials: KW
authors.lastname: Washio
authors.affiliation: Division of Innovative Diabetes Treatment, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: ykusu@hyo-med.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kusunoki
authors.affiliation: Radioisotope and Chemical Analysis Center, Laboratory Management Department, Sanwa Kagaku Kenkyusho Co. Ltd., 363 Shiosaki Hokusei Town Inabe, Mie 511-0406, Japan.
authors.forename: Takayo
authors.initials: T
authors.lastname: Murase
authors.affiliation: Pharmacological Study Group, Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co. Ltd., 363 Shiosaki Hokusei Town Inabe, Mie 511-0406, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Osugi
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Ohigashi
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Sukenaga
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ochi
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Katsuno
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Namba
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000201:enzymology*; D007333:Insulin Resistance; D008297:Male; D013058:Mass Spectrometry; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D052242:Adiponectin; D019820:Xanthine; D014527:Uric Acid; D002097:C-Reactive Protein; D014968:Xanthine Dehydrogenase
keywords: Adiponectin; Inflammation; Insulin resistance; Uric acid; Xanthine oxidoreductase