2型糖尿病患者尿核糖浓度显著高于正常
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中国科学院生物物理研究所,中国科学院生物物理研究所,中国科学院生物物理研究所,中国科学院生物物理研究所,北京大学第一医院,北京大学第一医院,北京大学第一医院,中国科学院生物物理研究所

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国家重点基础研究发展计划(973)(2012CB911000,2010CB912303),国家自然科学基金(31270868,31200601,81100610)和北京市自然科学基金(5112024)资助项目


The Abnormally High Level of Uric D-Ribose for Type-2 Diabetics
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Institute of Biophysics, Chinese Academy of Sciences,Institute of Biophysics, Chinese Academy of Sciences,Institute of Biophysics, Chinese Academy of Sciences,Institute of Biophysics, Chinese Academy of Sciences,Peking University First Hospital,,Peking University First Hospital,,Peking University First Hospital,,Institute of Biophysics, Chinese Academy of Sciences

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This work was supported by grants from National Basic Research Program of China (2012CB911000, 2010CB912303), The National Natural Science Foundation of China (31270868, 31200601, 81100610) and Beijing Municipal Natural Science Foundation (5112024)

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    摘要:

    自从Chevreul ME发现糖尿病患者尿液中的糖是葡萄糖,近200年的时间,糖尿病被视为一组以葡萄糖慢性增高为特征的代谢性疾病,而体内广泛存在的核糖与糖尿病之间的关系却被忽略.研究发现核糖可以降低血葡萄糖浓度,曾报道糖尿病患者可以口服核糖.本实验室前期工作表明,核糖能够迅速与蛋白质发生非酶促糖基化,形成具有强烈细胞毒性的糖基化终末产物(advanced glycation end products,AGEs),引起细胞(包括神经细胞)死亡.进一步的实验证明,虽然在给小鼠注射核糖时,血葡萄糖浓度有所降低,但是糖基化血清蛋白和AGEs均显著升高,说明核糖浓度的升高更容易使机体发生非酶促糖基化反应,产生AGEs,从而造成危害.本文采用1-(4-羧基苯基)-3-甲基-5-吡唑酮(MOPBA)结合高效液相色谱,对明确诊断的2型糖尿病患者(n = 30)和同龄健康人(n = 30)尿核糖进行了定量分析,结果显示,MOPBA-核糖衍生物与尿核糖浓度之间呈线性相关(r2=0.999),回收率达99%.经质谱分析显示,HPLC分离的糖尿病患者尿样品中含569.19 u MOPBA衍生物峰(核糖,C27H29N4O10)和599.20 u MOPBA衍生物峰(葡萄糖,C28H31N4O11).2型糖尿病组尿核糖浓度(男性:(134.28±35.09) μmol/L;女性:(97.33±23.68) μmol/L)显著高于正常对照组(男性:(35.99±5.64) μmol/L;女性:(33.72±6.27) μmol/L) (P < 0.001),同时,其尿葡萄糖浓度也显著高于正常对照(P < 0.001).糖尿病患者尿核糖显著高于正常人的现象提示,2型糖尿病不但葡萄糖代谢异常,同时核糖代谢也发生了异常.

    Abstract:

    In 1815, the French chemist Michel Eug?ne Chevreul (1786-1889) discovered that the sweetness in the urine of diabetics comes from grape sugar or D-glucose. Diabetes mellitus (DM) is considered as a group of metabolic diseases characterized by hyperglycemia (high concentration of blood D-glucose) resulting from defects in insulin secretion, insulin action, or both. On the other hand, D-ribose as an energetic enhancer was found to decrease the concentration of blood D-glucose, and thus "Oral administration of D-ribose in diabetes mellitus" was ever described by Steinberg and colleagues (1970). As described previously in this laboratory, D-ribose rapidly glycates proteins, such as BSA, neuronal Tau and α-synuclein, producing advanced glycation end products (AGEs) with severe cytotoxicity, leading to dysfunction and cell death, in vitro and in vivo. Intraperitoneal injection of D-ribose into mice significantly increases their glycated serum protein and blood AGEs though the concentration of D-glucose became slightly decreased, suggesting that D-ribose is much easier to produce AGEs than D-glucose in vivo. Here, using 4-(3-Methyl-5-oxo-2-pyrazolin-1-yl) benzoic acid (MOPBA) coupled with HPLC, we determined the concentration of uric D-ribose of type 2 diabetic patients (n=30) and the age-matched healthy controls (n=30). The results show that the yield of the derivative of MOPBA-ribose is linearly correlated with the concentration of D-ribose (r2=0.999) with a recovery of 99%. The isolated fractions of D-ribose and D-glucose from urine of type 2 diabetic patients through HPLC were analyzed by mass spectrometry, and the results showed that the fractions contained 569.19 u compound (C27H29N4O10, D-ribose), and 599.20 u compound (C28H31N4O11, D-glucose) respectively. The concentration of uric D-ribose of Type 2 diabetics (male (134.28±35.09) μmol/L, female (97.33±23.68) μmol/L) was significantly (P < 0.001) higher than that of the age-matched healthy control (male (35.99±5.64) μmol/L, female (33.72±6.27) μmol/L). Under the experimental conditions, the uric D-glucose level of the patients was also markedly (P < 0.001) higher than the control. Further analyses showed a marked increase in the level of uric D-ribose from either male (P < 0.001) or female (P < 0.001), but a significant difference of the uric levels between male and female could not be observed (P > 0.05). The high levels of uric D-ribose and D-glucose of the patients suggest that type 2 diabetic patients are not only suffered from D-glucose metabolism disorders, but also from D-ribose metabolism disorders.

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苏 涛,辛亮,赫英舸,魏艳,宋宜祥,黎巍威,王学美,赫荣乔.2型糖尿病患者尿核糖浓度显著高于正常[J].生物化学与生物物理进展,2013,40(9):816-825

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历史
  • 收稿日期:2013-07-18
  • 最后修改日期:2013-08-17
  • 接受日期:2013-08-26
  • 在线发布日期: 2013-09-16
  • 出版日期: 2013-09-20