Lixandru D, Alexandru P, Mihai A, Roşca A, Ionescu-Tîrgovişte C, Braşoveanu L I, Manuel-Y-Keenoy B
a University of Medicine and Pharmacy "Carol Davila" , Bucharest , Romania.
b Department of Molecular Cell Biology , Institute of Biochemistry of the Romanian Academy , Bucharest , Romania.
Free Radic Res. 2017 Jun;51(6):604-615. doi: 10.1080/10715762.2017.1344983. Epub 2017 Jul 13.
To investigate peripheral blood monocytes/macrophages (Mo/Mᴓ) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.
One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).
Paraoxonase 2 activity in Mo/Mᴓ was significantly lower in type 2 diabetes patients (0.042 ± 0.044 vs 0.165 ± 0.133U lactonase activity/mg protein in controls, p < .0005) and decreased in the obese in all groups. It was inversely correlated to parameters of adiposity (BMI and Waist Circumference), of glucose control (blood glucose, fructosamine and HbA) and insulin resistance (HOMA-IR). In multivariate regression models, 15-34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S- (to 82 ± 18% of the cells incubated with serum, S+) and PON2 activity (from 0.524 ± 0.061 in S - to 0.298 ± 0.048 U/mg protein). In contrast, when LDL was added, the RB remained lower (61 ± 12% of S+, p = .03) and PON2 higher (0.580 ± 0.030 U/mg protein, p = .003).
The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.
研究糖尿病患者外周血单核细胞/巨噬细胞（Mo/Mᴓ）对氧磷酶2（PON2）的情况及其活性调节因素。
将118例新诊断的无并发症2型糖尿病患者与80名健康受试者在临床、生化和氧化应激参数方面进行比较。通过测量呼吸爆发（RB）和细胞内抗氧化酶PON2来确定外周血单核细胞（PBMNC）释放促氧化剂和中和促氧化剂的能力。在分化的单核细胞系（dU937）上进行体外实验，该细胞系先经历血清剥夺，然后添加分离的脂蛋白（极低密度脂蛋白或低密度脂蛋白）。
2型糖尿病患者Mo/Mᴓ中的对氧磷酶2活性显著降低（0.042±0.044与对照组中0.165±0.133U内酯酶活性/毫克蛋白相比，p<0.0005），且在所有组的肥胖患者中均降低。它与肥胖参数（体重指数和腰围）、血糖控制参数（血糖、果糖胺和糖化血红蛋白）以及胰岛素抵抗（稳态模型评估胰岛素抵抗指数）呈负相关。在多变量回归模型中，糖尿病可解释15%至34%的PON2变异。体外添加极低密度脂蛋白可使血清剥夺的dU937细胞的RB恢复正常，S-（恢复至与血清孵育的细胞S+的82±18%）以及PON2活性（从S-中的0.524±0.061U/mg蛋白恢复至0.298±0.048U/mg蛋白）。相反，添加低密度脂蛋白时，RB仍较低（S+的61±12%，p=0.03）且PON2较高（0.580±0.030U/mg蛋白，p=0.003）。
2型糖尿病中观察到的单核细胞/巨噬细胞PON2酶活性降低不能完全由腹型肥胖和胰岛素抵抗来解释。需要确定其潜在的分子机制。
