Increased Glycation and Oxidative Damage to Apolipoprotein B100 of LDL Cholesterol in Patients With Type 2 Diabetes and Effect of Metformin
Increased Glycation and Oxidative Damage to Apolipoprotein B100 of LDL Cholesterol in Patients With Type 2 Diabetes and Effect of Metformin
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DOI：
10.2337/db09-1455
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发表时间：
2010-04-01
期刊：
影响因子：
7.7
通讯作者：
Thornalley, Paul J.
中科院分区：
文献类型：
--
作者：
Rabbani, Naila;Chittari, Madhu Varma;Thornalley, Paul J.
结论：本研究的目的是调查2型糖尿病患者（包括接受二甲双胍治疗的患者）的LDL载脂蛋白B100是否受到糖化、氧化和硝化的损害增加，研究设计和方法：本研究招募了32名2型糖尿病患者和21名健康对照受试者; 13名糖尿病患者接受二甲双胍治疗（中位剂量：1.50克/天）。通过超离心从静脉血浆中分离LDL，脱脂，消化，并通过稳定同位素稀释分析串联质谱法分析蛋白质糖化、氧化和硝化加合物。来自2型糖尿病患者的LDL的载脂蛋白B100的AGEs-晚期糖化终产物（AGE）含量高于来自健康受试者：精氨酸衍生的AGE，15.8mol%对5.3mol%（P < 0.001）;和赖氨酸衍生的AGE，2.5mol%对1.5mol%（P < 0.05）。氧化损伤，主要是蛋氨酸亚砜残基，也增加：2.5对1.1摩尔当量（P < 0.001）。3-硝基酪氨酸含量降低：0.04mol% vs.0.12mol%（P < 0.05）。在接受二甲双胍治疗的糖尿病患者中，精氨酸衍生的AGE和甲硫氨酸亚砜低于未接受二甲双胍治疗的患者：分别为19.3与8.9 mol%（P < 0.01）和2.9与1.9 mol%（P < 0.05）; 3-硝基酪氨酸含量较高：0.10与0.03 mol%（P < 0.05）。果糖基赖氨酸残留量与空腹血糖呈正相关。精氨酸衍生的AGE残基含量之间存在相关性，并与蛋氨酸亚砜呈正相关。结论2型糖尿病患者的精氨酸衍生的AGE和LDL载脂蛋白B100的氧化损伤增加。接受二甲双胍治疗的患者中该值较低，这可能有助于降低氧化损伤、致动脉粥样硬化性和心血管疾病。糖尿病59：1038-1045，2010
OBJECTIVE-The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy.RESEARCH DESIGN AND METHODS-For this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry.RESULTS-Advanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyllysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide.CONCLUSIONS-Patients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease. Diabetes 59:1038-1045, 2010