Clore J N, Harris P A, Li J, Azzam A, Gill R, Zuelzer W, Rizzo W B, Blackard W G
Department of Internal Medicine, Virginia Commonwealth University, Richmond 23298, USA.
Metabolism. 2000 Feb;49(2):232-8. doi: 10.1016/s0026-0495(00)91455-0.
The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic-euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 +/- 7.5 to 64.6 +/- 9.0 microU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% +/- 0.3% to 21.7% +/- 0.4%, P < .05) and decreases in 18:0 (6.2% +/- 0.5% to 5.1% +/- 0.4%, P = .01), long-chain n-3 fatty acids (1.7% +/- 0.2% to 1.4% +/- 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% +/- 0.8% to 8.0% +/- 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man.
众所周知，骨骼肌细胞膜磷脂（PLs）的脂肪酸组成会影响人体的胰岛素反应性。我们最近发现，骨骼肌膜中磷脂酰胆碱（PC）而非磷脂酰乙醇胺（PE）的脂肪酸组成在这种关系中尤为重要。在动物模型中改变PL脂肪酸组成的研究表明会诱发胰岛素抵抗。然而，要确定人体胰岛素敏感性的变化是否与骨骼肌膜PL脂肪酸组成的变化相关则更为困难。使用已知可在人体诱发胰岛素抵抗的烟酸（NA），对9名正常受试者在治疗前后进行了为期1个月的研究。使用三步高胰岛素-正常血糖钳夹技术，将股外侧肌活检样本中PC和PE的骨骼肌膜脂肪酸组成与胰岛素反应性进行关联分析。NA治疗使半数最大胰岛素浓度（[ED50]从52.0±7.5微单位/毫升增至64.6±9.0微单位/毫升，增加了25%，P<.05），这与外周胰岛素敏感性降低一致。NA给药后，还观察到PC的脂肪酸组成有显著变化，但PE没有。16:0的百分比增加（从21%±0.3%增至21.7%±0.4%，P<.
