Yki-Järvinen H, Taskinen M R
Second Department of Medicine, University of Helsinki, Finland.
Diabetes. 1988 Sep;37(9):1271-8. doi: 10.2337/diab.37.9.1271.
We tested the hypothesis that the previously observed association among hypertriglyceridemia, hyperinsulinemia, and insulin resistance could be explained by a defect in insulin's antilipolytic effect. Insulin action was measured in 10 nondiabetic and 8 diabetic patients with hypertriglyceridemia (fasting plasma triglyceride 800 +/- 154 and 1105 +/- 445 mg/dl, respectively, P NS; fasting plasma glucose 99 +/- 3 and 161 +/- 12 mg/dl, respectively, P less than .001) and in 8 weight-matched normolipemic nondiabetic individuals (fasting plasma triglyceride and glucose 110 +/- 21 and 91 +/- 3 mg/dl). The slope of the decay in plasma free fatty acid (FFA) during insulin infusion was used as an index of insulin's antilipolytic effect. Insulin stimulation of glucose uptake in vivo during intravenous hyperinsulinemic clamp and in vitro in adipocytes were measures of insulin's glucoregulatory action. Both glucoregulatory and antilipolytic effects were similarly reduced in both hypertriglyceridemic groups compared with normal subjects. The plasma triglyceride concentration correlated positively with the slope of FFA suppression by insulin (r = .81, P less than .0001) and the fasting FFA concentration (r = .65, P less than .0001). In multiple linear regression analysis, insulin's antilipolytic effect and the fasting FFA concentration explained 83% of the variation in the plasma triglyceride concentration. These associations were independent of insulin's glucoregulatory effect and the fasting plasma insulin concentration. The data indicate that patients with endogenous hypertriglyceridemia are resistant to both the antilipolytic and glucoregulatory actions of insulin and that increased flux of FFA as a result of the latter, rather than hyperinsulinemia, is responsible for elevation of very-low-density lipoprotein production.(ABSTRACT TRUNCATED AT 250 WORDS)
我们检验了这样一个假设，即先前观察到的高甘油三酯血症、高胰岛素血症和胰岛素抵抗之间的关联可以通过胰岛素抗脂解作用缺陷来解释。在10名非糖尿病和8名患有高甘油三酯血症的糖尿病患者中测量了胰岛素作用（空腹血浆甘油三酯分别为800±154和1105±445mg/dl，P无显著差异；空腹血浆葡萄糖分别为99±3和161±12mg/dl，P<0.001），以及8名体重匹配的血脂正常的非糖尿病个体（空腹血浆甘油三酯和葡萄糖分别为110±21和91±3mg/dl）。胰岛素输注期间血浆游离脂肪酸（FFA）衰减的斜率用作胰岛素抗脂解作用的指标。静脉内高胰岛素钳夹期间体内以及脂肪细胞体外胰岛素刺激的葡萄糖摄取是胰岛素葡萄糖调节作用的指标。与正常受试者相比，两个高甘油三酯血症组的葡萄糖调节和抗脂解作用均同样降低。血浆甘油三酯浓度与胰岛素抑制FFA的斜率呈正相关（r = 0.81，P<0.0001）以及空腹FFA浓度呈正相关（r = 0.65，P<0.0001）。在多元线性回归分析中，胰岛素的抗脂解作用和空腹FFA浓度解释了血浆甘油三酯浓度变化的83%。这些关联独立于胰岛素的葡萄糖调节作用和空腹血浆胰岛素浓度。数据表明，内源性高甘油三酯血症患者对胰岛素的抗脂解和葡萄糖调节作用均有抵抗，并且由于后者导致的FFA通量增加而非高胰岛素血症是极低密度脂蛋白产生增加的原因。（摘要截短于250字）
