ACCELERATED AGE-RELATED BROWNING OF HUMAN COLLAGEN IN DIABETES-MELLITUS
ACCELERATED AGE-RELATED BROWNING OF HUMAN COLLAGEN IN DIABETES-MELLITUS
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DOI：
10.1073/pnas.81.2.583
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
CERAMI, A
中科院分区：
文献类型：
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作者：
MONNIER, VM;KOHN, RR;CERAMI, A
在糖尿病中加速的非酶糖基化反应是储存食品中发生的美拉德或非酶布朗宁反应的第一步。葡萄糖-蛋白质加合物重排和脱水形成棕色和荧光色素，其可作为交联剂，导致蛋白质溶解度降低和机械性质改变。在透镜晶体蛋白中发现了表明这一过程发生在体内的证据。随着年龄和糖尿病，胶原蛋白的非酶糖基化和不溶性增加，这一观察结果导致了对人胶原蛋白可能的布朗宁的研究。用胶原酶消化不溶性人硬脑膜胶原。测量溶解的材料在350 nm处的吸光度和在440 nm处的荧光（在370 nm处激发）。随着年龄的增长，黄色和荧光物质的量呈线性增加。从3名I型糖尿病患者和一名年轻的II型糖尿病患者尸检中获得的样本显示荧光增强，其吸光度值相当于非糖尿病患者中发现的发色团数量的两倍（P < 0.025）。来自老年人和糖尿病患者的胶原加合物的吸收和荧光光谱与在体外用葡萄糖进行非酶布朗宁的胶原样品的吸收和荧光光谱相同。这些胶原加合物的结构是未知的。然而，它们在全身的可能发生可以解释I型糖尿病患者中动脉硬化、关节活动度降低和微血管并发症严重程度之间的相关性。
The nonenzymatic glycosylation reaction that is accelerated in diabetes is the 1st step of the Maillard or nonenzymatic browning reaction that occurs in stored food. The glucose-protein adduct rearranges and dehydrates to form brown and fluorescent pigments, which can act as crosslinks, resulting in decreased protein solubility and altered mechanical properties. Evidence suggesting that this process occurs in vivo has been found in lens crystallins. The observation that nonenzymatic glycosylation and insolubility increases in collagen with age and diabetes led to an investigation of the possible browning of human collagen. Insoluble human dura mater collagen was digested with collagenase. Absorbance at 350 nm and fluorescence at 440 nm (excitation at 370 nm) of the solubilized material was measured. A linear increase in the amounts of yellow and fluorescent material was observed with age. Samples obtained at autopsy from 3 type I diabetics and a young type II diabetic showed increased fluorescence and had absorbance values that corresponded to the amount of chromophore found in nondiabetics twice their age (P < 0.025). The collagen adducts from aged and diabetic individuals had absorption and fluorescence spectra identical to those of collagen samples that underwent nonenzymatic browning with glucose in vitro. The structure of these collagen adducts is unknown. However, their likely occurrence throughout the body could explain the correlation between arterial stiffening, decreased joint mobility, and the severity of microvascular complications in type I diabetics.