Institute of Cardiology, G. d'Annunzio University-Chieti, Italy.
Vascul Pharmacol. 2011 Mar-Jun;54(3-6):68-74. doi: 10.1016/j.vph.2011.03.005. Epub 2011 Mar 29.
Diabetes-induced micro- and macrovascular complications are the major causes of morbidity and mortality in diabetic patients. While hyperglycemia is a key factor for the pathogenesis of diabetic microvascular complications, it is only one of the multiple factors capable of increasing the risk of macrovascular complications. Hyperglycemia induces vascular damage probably through a single common pathway - increased intracellular oxidative stress - linking four major mechanisms, namely the polyol pathway, advanced glycation end-products (AGEs) formation, the protein kinase C (PKC)-diacylglycerol (DAG) and the hexosamine pathways. In addition, in conditions of insulin resistance, i.e., preceding the onset of type 2 diabetes, the phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway is selectively inhibited, while the mitogen activated protein (MAP)-kinase pathway remains largely unaffected, thus allowing compensatory hyperinsulinemia to elicit pro-atherogenic events in vascular smooth muscle and endothelial cells, including increased cell proliferation, and the expression of plasminogen activator inhibitor-1, as well as of proinflammatory cytokines and endothelial adhesion molecules.
糖尿病引起的微血管和大血管并发症是糖尿病患者发病率和死亡率的主要原因。虽然高血糖是糖尿病微血管并发症发病机制的关键因素，但它只是增加大血管并发症风险的众多因素之一。高血糖可能通过单一的共同途径——增加细胞内氧化应激——将四种主要机制联系起来，即多元醇途径、晚期糖基化终产物（AGEs）形成、蛋白激酶 C（PKC）-二酰基甘油（DAG）和己糖胺途径，导致血管损伤。此外，在胰岛素抵抗的情况下，即在 2 型糖尿病发病之前，磷酸肌醇（PI）3-激酶（PI3K）/Akt 途径被选择性抑制，而丝裂原激活蛋白（MAP）-激酶途径基本不受影响，从而允许代偿性高胰岛素血症在血管平滑肌和内皮细胞中引发促动脉粥样硬化事件，包括细胞增殖增加、纤溶酶原激活物抑制剂-1 以及促炎细胞因子和内皮细胞黏附分子的表达。
