Frénais R, Nazih H, Ouguerram K, Maugeais C, Zaïr Y, Bard J M, Charbonnel B, Magot T, Krempf M
Human Nutrition Research Center, INSERM, U-539, Hôtel Dieu, 44093 Nantes Cedex 01, France.
J Clin Endocrinol Metab. 2001 May;86(5):1962-7. doi: 10.1210/jcem.86.5.7480.
The aim of this study was to delineate the role of lipoprotein lipase (LPL) activity in the kinetic alterations of high density lipoprotein (HDL) metabolism in patients with type II diabetes mellitus compared with controls. The kinetics of HDL were studied by endogenous labeling of HDL apolipoprotein AI (HDL-apo AI) using a primed infusion of D(3)-leucine. The HDL-apo AI fractional catabolic rate (FCR) was significantly increased (0.32 +/- 0.07 vs. 0.23 +/- 0.05 pool/day; P < 0.01), and HDL composition was changed [HDL cholesterol, 0.77 +/- 0.16 vs. 1.19 +/- 0.37 mmol/L (P < 0.05); HDL triglycerides, 0.19 +/- 0.12 vs. 0.10 +/- 0.03 mmol/L (P < 0.05)] in diabetic patients compared with healthy subjects. HDL-apo AI FCR was correlated to plasma and HDL triglyceride concentrations (r = 0.82; P < 0.05 and r = 0.80; P < 0.05, respectively) and to homeostasis model assessment (r = 0.78; P < 0.05). Postheparin plasma LPL activity was decreased in type II diabetes (6.8 +/- 2.8 vs. 18.1 +/- 5.2 micromol/mL postheparin plasma.h; P < 0.005) compared with that in healthy subjects and was correlated to the FCR of HDL-apo AI (r = -0.63; P < 0.05). LPL activity was also correlated with HDL cholesterol (r = 0.78; P < 0.05), plasma and HDL triglycerides (r = -0.87; P < 0.005 and r = -0.83; P < 0.05, respectively), and homeostasis model assessment (r = -0.79; P < 0.05). In addition, the LPL to hepatic lipase ratio was correlated with the catabolic rate of HDL (r = -0.76; P < 0.06). These results suggest that a decrease in the LPL to hepatic lipase ratio in type II diabetes mellitus, mainly related to lowered LPL activity, could induce an increase in HDL catabolism. These alterations in HDL kinetics in type II diabetes proceed to some extent from changes in their composition, probably linked to an increase in triglyceride transfer from very low density lipoprotein particles, in close relationship with LPL activity and resistance to insulin.
本研究的目的是阐明脂蛋白脂肪酶（LPL）活性在II型糖尿病患者高密度脂蛋白（HDL）代谢动力学改变中的作用，并与对照组进行比较。通过使用D(3)-亮氨酸的预充式输注对HDL载脂蛋白AI（HDL-apo AI）进行内源性标记来研究HDL的动力学。与健康受试者相比，糖尿病患者的HDL-apo AI分数分解代谢率（FCR）显著升高（0.32±0.07对0.23±0.05池/天；P<0.01），且HDL组成发生改变[HDL胆固醇，0.77±0.16对1.19±0.37 mmol/L（P<0.05）；HDL甘油三酯，0.19±0.12对0.10±0.03 mmol/L（P<0.05）]。HDL-apo AI FCR与血浆和HDL甘油三酯浓度相关（分别为r = 0.82；P<0.05和r = 0.80；P<0.05），并与稳态模型评估相关（r = 0.78；P<0.05）。与健康受试者相比，II型糖尿病患者肝素后血浆LPL活性降低（肝素后血浆6.8±2.8对18.1±5.2 μmol/mL·h；P<0.005），且与HDL-apo AI的FCR相关（r = -0.63；P<0.05）。LPL活性还与HDL胆固醇（r = 0.78；P<0.05）、血浆和HDL甘油三酯（分别为r = -0.87；P<0.005和r = -0.83；P<0.05）以及稳态模型评估（r = -0.79；P<0.05）相关。此外，LPL与肝脂肪酶的比值与HDL的分解代谢率相关（r = -0.76；P<0.06）。这些结果表明，II型糖尿病中LPL与肝脂肪酶比值的降低，主要与LPL活性降低有关，可能会导致HDL分解代谢增加。II型糖尿病中HDL动力学的这些改变在一定程度上源于其组成的变化，这可能与极低密度脂蛋白颗粒中甘油三酯转移增加有关，与LPL活性和胰岛素抵抗密切相关。
