Disordered Glucose Levels Are Associated with Xanthine Oxidase Activity in Overweight Type 2 Diabetic Women

Abstract

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of β-cell function (HOMA-β), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.

Metabolite Profiling in a Diet-Induced Obesity Mouse Model and Individuals with Diabetes: A Combined Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy Study

“…However, none of these genera was found to associate with xanthine in human plasma in the GutsyAtlas data [ 32 ]. The reduced xanthine concentrations upon HFD exposure are more in line with reports of increased activity of the purine catabolism enzymes xanthine oxidoreductase and xanthine oxidase in serum of individuals with obesity, metabolic syndrome and T2D [ 33 , 34 , 35 ]. In our study, pathway analysis indicated altered purine metabolism at both 1 and 8 weeks of HFD exposure in mice, and also in individuals with T2D.…”

Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application

“…T2DM leads to excessive ROS production through various pathways. Early research suggested that glucose could directly stimulate excessive ROS production ( Du et al, 1999 ), but later studies found that high glucose (HG) activates various enzymatic cascades in mitochondria ( Rizwan et al, 2020 ), including the activation of NADPH oxidase ( Jansen et al, 2013 ), NO synthase uncoupling ( Sasaki et al, 2008 ), and the stimulation of xanthine oxidase ( Hernandez-Hernandez et al, 2022 ). Similarly, elderly individuals often have comorbidities such as dyslipidemia and hypertension, which can also induce ROS production.…”

Phytochemical Profiling, Antioxidant, Antidiabetic, and Admet Study of Diospyros Mespiliformis Hochst. Ex A. Dc. (Ebenaceae) Leaf

“…Thus, further revealing the flexibility of the complex and possible XO inhibition. Additionally, high XO activity was reported to be associated with type 2 diabetes [60]. Therefore, a decrease in its activity might be associated with antidiabetic activity via alleviation of oxidative stress.…”