Lewis G F, Uffelman K D, Szeto L W, Steiner G
Department of Medicine, University of Toronto, Ontario, Canada.
Diabetes. 1993 Jun;42(6):833-42. doi: 10.2337/diab.42.6.833.
The effects of short-term hyperinsulinemia on the production of both VLDL triglyceride and VLDL apoB were determined semiquantitatively before and during a 6-h euglycemic hyperinsulinemic clamp (40 mU.m-2 x min-1) in 17 women (8 chronically hyperinsulinemic obese, BMI = 35.7 kg/m2; 9 normal weight, BMI = 22.5 kg/m2). During acute hyperinsulinemia, plasma FFA decreased by approximately 95% within 1 h in both groups. VLDL triglyceride production decreased 66% in the control subjects (P = 0.0003) and 67% in obese subjects (P = 0.0003). ApoB production decreased 53% in control subjects (P = 0.03) but only 8% in obese (NS). Plasma triglycerides decreased by 40% from baseline in control subjects (P < 0.0001) but only by 10% in obese subjects (P = NS). Despite the similar decrease in triglyceride and apoB production in control subjects, VLDL particle size (triglyceride-to-apoB ratio) decreased with hyperinsulinemia (P = 0.003). In obese subjects, despite a decrease in triglyceride production similar to that in control subjects but no change in apoB production, VLDL size did not change appreciably. Acute hyperinsulinemia in humans: 1) suppresses plasma FFA equally in control and obese subjects at this high dose of insulin; 2) inhibits VLDL triglyceride production equally in control and obese subjects, perhaps secondary to the decrease in FFA; 3) inhibits VLDL apoB production in control but less so in obese subjects, suggesting that obese subjects may be resistant to this effect of insulin; 4) decreases plasma triglyceride and VLDL particle size in control subjects, reflecting either stimulation of LPL activity or a greater relative decrease in triglyceride to apoB production; and 5) does not decrease plasma triglyceride or VLDL size in obese subjects to the same extent as it does in control subjects. Thus, the insulin resistance of obesity affects some but not all aspects of VLDL metabolism.
在17名女性（8名慢性高胰岛素血症肥胖者，BMI = 35.7kg/m²；9名正常体重者，BMI = 22.5kg/m²）中，于6小时正常血糖高胰岛素钳夹试验（40mU·m⁻²·min⁻¹）前及试验期间，半定量测定短期高胰岛素血症对极低密度脂蛋白甘油三酯（VLDL甘油三酯）和极低密度脂蛋白载脂蛋白B（VLDL apoB）生成的影响。在急性高胰岛素血症期间，两组受试者血浆游离脂肪酸（FFA）在1小时内均下降约95%。对照组中VLDL甘油三酯生成下降66%（P = 0.0003），肥胖组下降67%（P = 0.0003）。对照组中载脂蛋白B生成下降53%（P = 0.03），而肥胖组仅下降8%（无统计学意义）。对照组血浆甘油三酯较基线下降40%（P < 0.0001），肥胖组仅下降10%（P = 无统计学意义）。尽管对照组中甘油三酯和载脂蛋白B生成下降相似，但高胰岛素血症时极低密度脂蛋白颗粒大小（甘油三酯与载脂蛋白B比值）下降（P = 0.003）。在肥胖受试者中，尽管甘油三酯生成下降与对照组相似，但载脂蛋白B生成无变化，极低密度脂蛋白大小无明显改变。人类急性高胰岛素血症：1）在这种高剂量胰岛素作用下，对照组和肥胖受试者血浆FFA均受到同等程度抑制；2）对照组和肥胖受试者中VLDL甘油三酯生成均受到同等程度抑制，可能继发于FFA下降；3）对照组中VLDL载脂蛋白B生成受到抑制，而肥胖受试者中抑制程度较小，提示肥胖受试者可能对胰岛素的这一作用有抵抗；4）对照组中血浆甘油三酯和极低密度脂蛋白颗粒大小下降，反映出脂蛋白脂肪酶（LPL）活性受到刺激或甘油三酯生成相对载脂蛋白B生成有更大程度下降；5）肥胖受试者中血浆甘油三酯或极低密度脂蛋白大小下降程度不及对照组。因此，肥胖的胰岛素抵抗影响极低密度脂蛋白代谢的某些方面，但并非全部。
