ARACHIDONIC ACID METABOLISM IN DIABETES

花生四烯酸在血小板和血浆中代谢的改变 血管内皮细胞可能参与了血管内皮细胞的形成。 血管疾病是中国人死亡和残疾的主要原因 糖尿病患者。我们的目标是考察 调节复合脂中花生四烯酸的释放，与 特别注意花生四烯酸的作用 乙醚类脂，在正常和高血糖环境下。我们将学习 花生四烯酸从磷脂中释放的途径 内皮细胞识别哪些前体脂类与之偶联 花生四烯酸氧化的特定途径。在动物身上 在糖尿病模型中，我们将研究增强的相关作用 血小板磷脂酶活性与花生四烯酸升高的比较 血栓素A_2产生量增加的酸含量 以糖尿病为特征。 我们将对糖尿病对健康的影响进行研究 花生四烯酸在三个组织水平上的代谢： 1)在破碎的细胞中，检测磷脂酶A2和转酰基酶 活跃性； 2)在培养中保持的细胞中，检查对 花生四烯酸动员途径及后续研究进展 转化为活性衍生物； 3)在实验动物中，将诱发糖尿病和 花生四烯酸的血小板代谢将受到关注 按顺序进行。 需要检验的具体假设是： 1)二酰基和醚键中的花生四烯酸 磷脂被选择性地招募到不同的氧合作用中 刺激时的通路； 2)脂氧合酶途径的产物可能 血小板花生四烯酸代谢的反馈调节 和内皮细胞； 3)糖尿病可改变脂氧合酶介导的程度 花生四烯酸的氧合作用及其生成速率和 内皮细胞使PAF失活；以及 4)至少部分改变的二十碳烷类化合物的形成 糖尿病可能反映了脂氧合酶反馈调节的改变- 花生四烯酸固定化及其衍生产物 环氧合酶本身。

Altered metabolism of arachidonic acid in both platelets and endothelial cells may contribute to the pathogenesis of the vascular disease that is a major cause of death and disability in diabetic patients. Our objectives are to examine the sites of regulation of arachidonec acid release from complex lipids, with particular attention to the role of arachidonic acid containing ether lipids, in normal and hyperglycemic settings. We shall study the pathways of arachidonic acid release from phospholipids in endothelial cells to identify which precursor lipids are coupled to specific pathways of arachidonic acid oxygenation. In an animal model of diabetes, we shall study the relative roles of enhanced platelet phospholipase activity compared to increased arachidonic acid content in the increased thromboxane A2 production characteristic of diabetes. We shall undertake, studies of the influence of diabetes on arachidonic acid metabolism at three levels of organization: 1) in broken cells, examining phospholipase A2 and transacylase activity; 2) in cells maintained in culture, examining the regulation of pathways of mobilization of arachidonate and subsequent transformation into active derivatives; 3) in experimental animals, in which diabetes will be induced and platelet metabolism of arachidonic acid will be followed sequentially. The specific hypothesis to be tested are: 1) that arachidonic acid found in diacyl- and that in ether-linked phospholipids is selectively recruited to different oxygenation pathways upon stimulation; 2) that the products of the lipoxygenase pathway may exert feedback regulation on arachidonic acid metabolism in platelets and endothelial cells; 3) that diabetes may alter the extent of lipoxygenase-mediated oxygenation of arachidonic acid and the rates of formation and inactivation of PAF by endothelial cells; and 4) that at least part of the altered formation of eicosanoids in diabetes may reflect altered feedback regulation by lipoxygenase- derived products on arachidonic acid mobilization as well as on cyclooxygenase itself.