Vlassara H, Brownlee M, Cerami A
Clin Chem. 1986 Oct;32(10 Suppl):B37-41.
Prolonged hyperglycemia is the primary metabolic abnormality responsible for the development of irreversible tissue damage in chronic diabetes. However, patients with similar levels of chronic hyperglycemia can differ markedly in their susceptibility to diabetic complications. Among the mechanisms by which hyperglycemia may lead to tissue damage, nonenzymatic glycosylation involves excessive chemical attachment of glucose to proteins without the involvement of enzymes. The early Amadori products, resembling hemoglobin A1c, slowly give rise to complex irreversible glycosylation adducts. Only these post-Amadori products accumulate in diabetic tissues over long periods. However, early nonenzymatic glycosylation or Amadori product formation can alter such physiological processes as enzyme activity or binding of regulatory molecules. Advanced glycosylation end products can covalently trap extravasated serum proteins to the extravascular matrix, and thus may contribute to capillary closure in the retina and glomerulus, and to arterial narrowing in the coronary, cerebral, and peripheral circulation. Although a macrophage receptor system may antagonize this glycosylation-mediated accumulation of proteins by recognizing and ingesting those proteins with advanced glycosylation end products, excessive formation of those proteins in diabetes may saturate the capacity of the macrophage removal system.
长期高血糖是导致慢性糖尿病不可逆组织损伤的主要代谢异常。然而，慢性高血糖水平相似的患者对糖尿病并发症的易感性可能有显著差异。在高血糖可能导致组织损伤的机制中，非酶糖基化涉及葡萄糖在无酶参与的情况下过度化学附着于蛋白质。早期的阿马多里产物类似于糖化血红蛋白A1c，会缓慢产生复杂的不可逆糖基化加合物。只有这些阿马多里后期产物会在糖尿病组织中长期积累。然而，早期非酶糖基化或阿马多里产物的形成会改变诸如酶活性或调节分子结合等生理过程。晚期糖基化终产物可将渗出的血清蛋白共价捕获到血管外基质，从而可能导致视网膜和肾小球的毛细血管闭塞，以及冠状动脉、脑循环和外周循环中的动脉狭窄。尽管巨噬细胞受体系统可能通过识别和摄取带有晚期糖基化终产物的蛋白质来对抗这种糖基化介导的蛋白质积累，但糖尿病中这些蛋白质的过度形成可能会使巨噬细胞清除系统的能力饱和。
