METABOLIC HETEROGENEITY OF PLASMA VLDL & LDL IN DIABETES

本研究考察了血浆代谢途径的异质性， 人的低密度脂蛋白（VLDL）和低密度脂蛋白（LDL） 并评估这种异质性在以下疾病中的重要性： 糖尿病的脂质代谢 本研究的具体目的是检验以下假设：1） 血浆极低密度脂蛋白的TG-贫亚组分（SF 60-20）是代谢异质性的 通过直接合成和脱脂形成 密度较小的颗粒; 2）该亚组分作为前体 IDL和LDL池，并作为一个残余途径，通过它不完全 形成的和/或部分脱脂的VLDL颗粒从细胞中清除， 血浆; 3）LDL亚组分（sf 12-0）来源于 大VLDL和小VLDL以及直接合成为IDL和LDL; 4） 低密度脂蛋白中的载脂蛋白B源决定了密度范围和分解代谢， LDL颗粒率; 5）TG-穷人的代谢异质性 VLDL和LDL受以下因素的影响：a）apo-B合成速率，B）肝脏 TG与apo-B和可能的其它载脂蛋白（apo-C和 apo-E），c）VLDL去脂级联的效率，和d）VLDL去脂级联的效率。 内脏对残余颗粒的摄取。 VLDL和LDL代谢的动力学参数是利用 脉冲注射放射性标记的VLDL 1（Sf 400-100）、VLDL 3（sf 60-20）和 LDL（sf 12-0）。 然后将这些数据用于开发多房室模型 描述代谢事件的模型。 研究在健康的 志愿者建立控制数据。 VLDL或LDL通道的调节 在高或低碳水化合物饮食的正常受试者中进行评估 以及遗传性高脂血症患者。 最后 非胰岛素依赖型糖尿病患者发生的流产， 没有高脂血症，以及这些异常与高脂血症的关系。 代谢概况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.