King G L, Brownlee M
Vascular Cell Biology Section, Joslin Diabetes Research Center, Boston, Massachusetts, USA.
Endocrinol Metab Clin North Am. 1996 Jun;25(2):255-70. doi: 10.1016/s0889-8529(05)70324-8.
In this article, the cellular and molecular mechanisms of diabetic complications have been reviewed. Hyperglycemia-induced mechanisms that may induce vascular dysfunction in specific sites of diabetic microvascular damage include increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol and the subsequent activation of specific PKC isoforms, and accelerated nonenzymatic formation of advanced glycation endproducts. Several of these mechanisms may be responsible for the potentially damaging overproduction of reactive oxygen species observed with hyperglycemia. Each of these mechanisms may contribute to the known pathophysiologic features of diabetic complications by a number of mechanisms, including the upregulation of cytokines and growth factors. Diabetic macrovascular disease may arise more from insulin resistance than from hyperglycemia, and the authors speculate that this may reflect a selective loss of insulin-dependent vascular homeostasis.
在本文中，对糖尿病并发症的细胞和分子机制进行了综述。高血糖诱导的机制可能在糖尿病微血管损伤的特定部位诱发血管功能障碍，这些机制包括多元醇途径通量增加、细胞氧化还原状态改变、二酰甘油形成增加以及随后特定蛋白激酶C亚型的激活，还有晚期糖基化终产物的非酶促形成加速。这些机制中的几种可能是高血糖时观察到的活性氧过度产生的潜在原因。这些机制中的每一种都可能通过多种机制导致糖尿病并发症的已知病理生理特征，包括细胞因子和生长因子的上调。糖尿病大血管疾病可能更多地源于胰岛素抵抗而非高血糖，作者推测这可能反映了胰岛素依赖性血管稳态的选择性丧失。
