Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover
Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover
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DOI：
10.1007/s00125-005-0066-6
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发表时间：
2006-02-01
期刊：
影响因子：
8.2
通讯作者：
Wu, G
中科院分区：
文献类型：
--
作者：
Marliss, EB;Chevalier, S;Wu, G
目的/假设：循环中增加的甲基精氨酸(MA)与代谢综合征有关，以解释内皮功能障碍和心血管疾病风险。含有MA的蛋白质是调节性的，并在分解代谢过程中释放它们。我们假设胰岛素抵抗状态下蛋白质周转增加有助于循环中MA的增加。材料和方法：我们对49名瘦、肥胖和老年受试者进行了高胰岛素、正常血糖和异氨基酸血症实验，测量了葡萄糖和蛋白质代谢的动力学。测定血浆非对称性二甲基精氨酸、对称性二甲基精氨酸和N-G-单甲基-L-精氨酸、血脂和体成分。结果：肥胖者和老年者存在糖代谢和蛋白质代谢的胰岛素抵抗。肥胖者的ADMA浓度比瘦的人高29-120%，老年人的ADMA浓度高34%。肥胖组SDMA分别比消瘦组和老年组高34%和20%。肥胖者的NMMA比瘦的人高32%。ADMA因性别不同而不同，男性高于男性，即肥胖男性为1.75倍，老年男性为1.27倍。吸收后ADMA(r=0.71)、SDMA(r=0.46)和NMMA(r=0.31)与蛋白质通量速率相关(P均<0.05)。所有三种MA均与钳夹葡萄糖输注率和摄取呈负相关(p<；0.001)。ADMA和SDMA与蛋白质净合成和钳制氨基酸输注率呈负相关(p<；0.05)。所有MA还与肥胖指数、空腹胰岛素和甘油三酯相关(p<；0.05)。结论/解释：肥胖、性别和年龄影响MA。肥胖者三种MA的升高和老年男性ADMA的升高与蛋白质周转增加和蛋白质代谢的胰岛素敏感性降低有关。这些相互关系可能会放大胰岛素抵抗和内皮功能障碍。
Aims/hypothesis: Increased circulating methylarginines ( MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. Materials and methods: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine ( ADMA), symmetrical dimethylarginine (SDMA), and N-G-monomethyl-L-arginine ( NMMA), lipids and body composition were measured. Results: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75 x in obese men and by 1.27 x in elderly men. Postabsorptive ADMA ( r= 0.71), SDMA ( r= 0.46), and NMMA ( r= 0.31) correlated ( all p< 0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake ( p< 0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates p< 0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides ( p< 0.05). Conclusions/ interpretation: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.