Malmström R, Packard C J, Caslake M, Bedford D, Stewart P, Yki-Järvinen H, Shepherd J, Taskinen M R
Department of Medicine, University of Helsinki, Finland.
Diabetes. 1998 May;47(5):779-87. doi: 10.2337/diabetes.47.5.779.
The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after an overnight fast (control study, n = 8), during inhibition of lipolysis with an antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic-hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was used to derive the kinetic constants. The mean rate of VLDL1 apo B production was 708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day (NS) during the acipimox study. Mean VLDL2 apo B production was significantly increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS). The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three studies. We conclude that acute lowering of FFAs does not change the overall production rate of VLDL particles, but there is a shift toward production of smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles secreted remained constant. Insulin acutely suppresses the total production rate of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1 particles. Based on these findings, we postulate that insulin has a direct suppressive effect on the production of VLDL apo B in the liver, independent of the availability of FFAs.
本研究的目的是检验胰岛素和阿西莫司（二者均可降低游离脂肪酸[FFA]的可利用性）对极低密度脂蛋白（VLDL）载脂蛋白（apo）B代谢的潜在差异影响。我们对8名健康男性（年龄40±4岁，体重指数25.8±0.9kg/m²，血浆甘油三酯1.30±0.12mmol/L）进行了研究，分别为过夜禁食后（对照研究，n = 8）、在用抗脂解剂阿西莫司抑制脂解期间（n = 8）以及在8.5小时血糖正常-高胰岛素血症状态下（n = 5）。在阿西莫司和胰岛素研究中，血浆FFA受到了相似程度的抑制（约70%的抑制率）。用²H₃-亮氨酸追踪VLDL1和VLDL2亚类（斯维德伯格漂浮率：60 - 400和20 - 60）中apo B的动力学，并用非稳态多室模型推导动力学常数。在对照研究开始时，VLDL1 apo B的平均生成速率为708±106mg/天，结束时为602±140mg/天。在胰岛素研究期间，该脂蛋白的生成降至248±93mg/天（与对照研究相比，P < 0.05），在阿西莫司研究期间降至375±92mg/天（无统计学意义）。在阿西莫司研究期间，VLDL2 apo B的平均生成显著增加（阿西莫司组为399±42mg/天，对照组为236±27mg/天，P < 0.05），而在胰岛素研究期间未增加（332±51mg/天，无统计学意义）。在所有三项研究中，VLDL1和VLDL2 apo B的分解代谢分数率相似。我们得出结论，FFA的急性降低不会改变VLDL颗粒的总体生成速率，但会转向生成更小、密度更高的VLDL2颗粒，因此，分泌的VLDL颗粒总量保持恒定。胰岛素通过减少富含甘油三酯的大颗粒VLDL1的生成，急性抑制VLDL apo B的总生成速率。基于这些发现，我们推测胰岛素对肝脏中VLDL apo B的生成具有直接抑制作用，与FFA的可利用性无关。
