METABOLIC HETEROGENEITY OF PLASMA VLDL & LDL IN DIABETES

这项研究考察了血浆代谢途径的异质性。 男性低密度脂蛋白和低密度脂蛋白 并评价了这种异质性在精神障碍中的重要性(S) 糖尿病患者的脂代谢。 这项研究的具体目的是检验假设：1) 血浆极低密度脂蛋白的贫甘油三酯亚组分(SF 60-20)在代谢上是不同的 由直接合成和脱脂反应形成的 指密度较低的颗粒；2)这个亚组分作为前驱物质 IDL和低密度脂蛋白的池，以及作为不完全通过的残余途径 形成的和/或部分脱脂的极低密度脂蛋白颗粒从 血浆；3)低密度脂蛋白亚组分(SF 12-0)来自于脂解 大小极低密度脂蛋白和直接合成IDL和低密度脂蛋白；4) 低密度脂蛋白中载脂蛋白B的来源决定了密度范围和分解代谢 低密度脂蛋白颗粒率；5)低密度脂蛋白的代谢异质性 极低密度脂蛋白和低密度脂蛋白受以下因素影响：a)载脂蛋白B合成率，b)肝脏 TG与载脂蛋白B和可能的其他载脂蛋白(apo-C和apo-C)的偶联 Apo-E‘s)，c)极低密度脂蛋白脱脂级联的效率，以及d) 内脏摄取残留颗粒。 测定了极低密度脂蛋白和低密度脂蛋白代谢的动力学参数 脉冲注射放射性标记的VLDL1(SF 400-100)、VLDL3(SF 60-20)和 低密度脂蛋白(SF 12-0)。然后，这些数据将被用来开发一个多间隔的 描述代谢事件的模型。研究是在健康人群中进行的 自愿建立控制数据。极低密度脂蛋白或低密度脂蛋白通道的调节 在正常受试者的高碳水化合物饮食或低碳水化合物饮食中进行评估 以及遗传性高甘油三酯血症患者。最后， 非胰岛素依赖型糖尿病患者中发生的流产 无高脂血症，以及这些异常与 定义了代谢特征和糖尿病控制的效果。

This study examines heterogeneity in the metabolic pathways of plasma very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in man and evaluates the importance of this heterogeneity in the disorder(s) of lipid metabolism in diabetes. The specific Aim of the study is to test the hypotheses: 1) that the TG-poor subfraction (sf 60-20) of plasma VLDL is metabolically heterogenous being formed by both direct synthesis and as a result of the delipidation of less dense particles; 2) that this subfraction serves as a precursor pool for IDL and LDL, and as a remnant pathway through which incompletely formed and/or partially delipidated VLDL particles are cleared from the plasma; 3) that the LDL subfraction (sf 12-0) is derived from lipolysis of both large and small VLDL and from direct synthesis into IDL and LDL; 4) that the apo-B source in LDL determines the density range and catabolic rate of LDL particles; 5) that the metabolic heterogeneity of the TG-poor VLDL and LDL is influenced by: a) the rate of apo-B synthesis, b) hepatic coupling of TG to apo-B and possibly other apolipoproteins (apo-C's and apo-E's), c) the efficiency of the VLDL delipidation cascade, and d) the splanchnic uptake of remnant particles. Kinetic parameters of VLDL and LDL metabolism are determined utilizing pulse injections of radiolabeled VLDL1 (Sf 400-100), VLDL3 (sf 60-20) and LDL (sf 12-0). The data will then be used to develop a multicompartmental model describing the metabolic events. Studies are performed in healthy volunteers to establish control data. Regulation of VLDL or LDL channeling is evaluated in normal subjects on either a high or low carbohydrate diet and in patients with genetic hypertriglyceridemias. Finally, the abormalities which occur in noninsulin-dependent diabetic patients with and without hyperlipidemia, and the relationship of these abnormalities to the metabolic profile and the effect of diabetic control are defined.