Differential regulation of hypoxanthine and xanthine by obesity in a general population

et al. 2021

Sci Rep

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Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

Section: Discussionsupporting

confidence: 69%

Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

et al. 2021

Sci Rep

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“…Significant associations between the plasma levels of hypoxanthine and xanthine, and between the plasma xanthine and XOR activity were also reported by another study conducted in the general population [29]. The plasma XOR activity and xanthine levels, but not the plasma hypoxanthine level, were correlated with the BMI, unlike the results of a previous study [29]. Hypoxanthine is a known marker of hypoxia [32,33] and a recent study revealed that the secretion of hypoxanthine from the adipose tissue increased in response to local hypoxia [34].…”

Section: Discussionsupporting

confidence: 71%

“…Since hypoxanthine is a precursor of xanthine, this association between hypoxanthine and xanthine might be easy to conceive. Significant associations between the plasma levels of hypoxanthine and xanthine, and between the plasma xanthine and XOR activity were also reported by another study conducted in the general population [29]. The plasma XOR activity and xanthine levels, but not the plasma hypoxanthine level, were correlated with the BMI, unlike the results of a previous study [29].…”

Section: Discussionmentioning

confidence: 46%

“…Thus, hypoxanthine and xanthine are precursors of uric acid. Recently, an association between plasma hypoxanthine levels and obesity/smoking was reported, and differential regulation of hypoxanthine and xanthine was reported in a Japanese general population [29]. However, the association between the levels of these purines and the XOR activity in patients with type 2 diabetes remained obscure.…”

Section: Introductionmentioning

confidence: 99%

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Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes: a cross-sectional study in a hospital setting

et al. 2020

Preprint

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Background Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species (ROS) and causes endothelial dysfunction. To explore the association of XOR and its substrate with the vascular complications in patients with type 2 diabetes mellitus (hereafter simply, diabetes), we measured the plasma XOR activity and plasma levels of xanthine and hypoxanthine in patients with type 2 diabetes. Materials and Methods Plasma XOR activity and the plasma levels of xanthine and hypoxanthine were measured, and their associations with the clinical parameters and vascular complications were investigated in 94 Japanese inpatients with type 2 diabetes. Results Both the plasma XOR activity and plasma xanthine levels were correlated with the serum uric acid level. The plasma XOR activity was correlated with the plasma xanthine level, but not the plasma hypoxanthine level. The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index (BMI), serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the serum high density lipoprotein cholesterol levels (HDL-C). The plasma XOR activity also showed a positive correlation with the serum triglyceride (TG) levels. Plasma xanthine was positively correlated with the Fib4-index. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. In addition, a negative correlation was observed between the plasma XOR activity and the duration of diabetes, and positive correlations were observed between the plasma XOR activity and the coefficient of variation of the R-R interval (CVR-R) and sensory nerve conduction velocity (SCV). Furthermore, the plasma XOR activity was found to be significantly decreased in patients with coronary artery disease. Conclusions The plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in patients with type 2 diabetes

“…This could possibly be attributable to the reutilization of hypoxanthine through the salvage pathway 20 xanthine might be easy to conceive. Significant associations between the plasma levels of hypoxanthine and xanthine, and between the plasma xanthine and XOR activity were also reported by another study conducted in the general population 23 . The plasma XOR activity and xanthine levels, but not the plasma hypoxanthine level, were correlated with the BMI, unlike the results of a previous study 23 .…”

Section: Discussionsupporting

confidence: 69%

Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

et al. 2020

Preprint

Self Cite

Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM).The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlatted with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease.Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.