2型糖尿病患者尿核糖浓度显著高于正常

The Abnormally High Level of Uric D-Ribose for Type-2 Diabetics

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.

In 1815, the French chemist Michel Eugene 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.