Taskinen M R, Packard C J, Shepherd J
Second Department of Medicine, University of Helsinki, Finland.
Diabetes. 1990 Sep;39(9):1017-27. doi: 10.2337/diab.39.9.1017.
Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
非胰岛素依赖型糖尿病（NIDDM）患者的血浆脂质和脂蛋白谱存在异常，这增加了缺血性心脏病的风险。本研究旨在检查NIDDM患者在治疗前和胰岛素治疗4周后的极低密度（VLDL）、中间密度（IDL）和低密度（LDL）脂蛋白的代谢行为。对一组7名已停用口服治疗1周的NIDDM患者进行了131I标记的VLDL1（斯维德伯格单位[Sf]60 - 400）和131I标记的VLDL2（Sf 20 - 60）载脂蛋白B（apoB）的基础周转率研究。这些受试者的VLDL1转运率高于正常水平，且apoB进入VLDL2密度范围的输入减少。这些观察结果与NIDDM患者过度产生VLDL甘油三酯但不产生apoB的假设一致。VLDL1和VLDL2以大致正常的速率转化为IDL并最终转化为LDL，尽管含apoB颗粒的脱脂途径表现出与对照受试者不同的特性。胰岛素治疗使血浆甘油三酯降低了38%，这与VLDL1质量下降41%相关（P < 0.01）。VLDL2受影响较小（降低19%，P < 0.05），IDL未改变，LDL下降17%（P < 0.05）。重复的代谢研究表明，胰岛素的主要作用是降低VLDL1 - apoB转运（从811降至488 mg/天）并增加VLDL2直接进入血浆的量（从182增至533 mg/天，P < 0.05）。VLDL产生的这些改变导致IDL和LDL中apoB动力学正常化。LDL的分解代谢率增加了19%（P < 0.05），而治疗前较高的该部分直接输入量减少。肝素后血浆脂蛋白脂肪酶（LPL）和肝脂肪酶水平不受胰岛素影响，尽管该激素确实增加了脂肪组织中的LPL。对脂肪酶活性缺乏影响与以下观察结果密切相关：胰岛素治疗对VLDL1、VLDL2和IDL中apoB的分解代谢率没有显著影响。
