Haller H, Drab M, Luft F C
Franz Volhard Clinic, Max Delbrück Center for Molecular Medicine, Virchow Clinic Berlin, Germany.
Clin Nephrol. 1996 Oct;46(4):246-55.
The small and large vessel disease associated with diabetes mellitus is responsible for its morbidity and mortality. Although much of the pathogenesis remains to be clarified, the role of hyperinsulinemia and hyperglycemia per se in the progression of vascular disease is beginning to emerge. Hyperinsulinemia increases the release of very low density lipoprotein (VLDL) and may also be responsible for the low HDL cholesterol levels in patients with diabetes. Hyperinsulinemia also contributes to increased blood pressure, which independently promotes vascular disease. High glucose concentrations have direct influence on intracellular signal transduction, including effects on sorbitol pathway and associated changes of pyridine nucleotides, the de novo synthesis of diacylglycerol with subsequent stimulation of protein kinase C, and possibly changes in the cellular generation of myoinositol. Hyperglycemia also exerts long-lasting changes in cellular function, which result from non-enzymatic glycosylation of matrix and membrane proteins with subsequent binding of these proteins to specific receptors. These receptors are termed the advanced glycosylation end-products (AGE) receptors. Their activation leads to an increased release of cytokines and growth factors including PDGF, interleukins, TNF-alpha, and TGF-beta, all of which may act concomitantly in the disease process.
与糖尿病相关的小血管和大血管疾病是其发病和死亡的原因。尽管许多发病机制仍有待阐明，但高胰岛素血症和高血糖本身在血管疾病进展中的作用已开始显现。高胰岛素血症会增加极低密度脂蛋白（VLDL）的释放，也可能是糖尿病患者高密度脂蛋白胆固醇水平低的原因。高胰岛素血症还会导致血压升高，而血压升高会独立促进血管疾病。高葡萄糖浓度对细胞内信号转导有直接影响，包括对山梨醇途径的影响以及吡啶核苷酸的相关变化、二酰基甘油的从头合成以及随后对蛋白激酶C的刺激，以及细胞内肌醇生成的可能变化。高血糖还会对细胞功能产生持久的改变，这是由于基质和膜蛋白的非酶糖基化以及这些蛋白随后与特定受体的结合所致。这些受体被称为晚期糖基化终产物（AGE）受体。它们的激活会导致细胞因子和生长因子的释放增加，包括血小板衍生生长因子（PDGF）、白细胞介素、肿瘤坏死因子-α和转化生长因子-β，所有这些因子可能在疾病过程中共同起作用。
