Storlien L H, Jenkins A B, Chisholm D J, Pascoe W S, Khouri S, Kraegen E W
Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Diabetes. 1991 Feb;40(2):280-9. doi: 10.2337/diab.40.2.280.
High levels of some but not all dietary fats lead to insulin resistance in rats. The aim of this study was to investigate the important determinants underlying this observation. Insulin action was assessed with the euglycemic clamp. Diets high in saturated, monounsaturated (omega-9), or polyunsaturated (omega-6) fatty acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain euglycemia at approximately 1000 pM insulin were 6.2 +/- 0.9, 8.9 +/- 0.9, and 9.7 +/- 0.4 mg.kg-1. min-1, respectively, versus 16.1 +/- 1.0 mg.kg-1.min-1 in chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat diet with long-chain omega-3 fatty acids from fish oils normalized insulin action (GIR 15.0 +/- 1.3 mg.kg-1.min-1). Similar replacement with short-chain omega-3 (alpha-linolenic acid, 18:3 omega 3) was ineffective in the polyunsaturated diet (GIR 9.9 +/- 0.5 mg.kg-1.min-1) but completely prevented the insulin resistance induced by a saturated-fat diet (GIR 16.0 +/- 1.5 mg.kg-1.min-1) and did so in both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was inversely correlated with mean muscle triglyceride accumulation (r = 0.95 and 0.86 for soleus and red quadriceps, respectively; both P less than 0.01). Furthermore, percentage of long-chain omega-3 fatty acid in phospholipid measured in red quadriceps correlated highly with insulin action in that muscle (r = 0.97). We conclude that 1) the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats; 2) impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose-fatty acid cycle involvement; and 3) long-chain omega-3 fatty acids in phospholipid of skeletal muscle may be important for efficient insulin action.
某些但并非所有膳食脂肪含量过高会导致大鼠出现胰岛素抵抗。本研究的目的是调查这一现象背后的重要决定因素。采用正常血糖钳夹技术评估胰岛素作用。富含饱和脂肪酸、单不饱和脂肪酸（ω-9）或多不饱和脂肪酸（ω-6）的饮食会导致严重的胰岛素抵抗；在胰岛素浓度约为1000 pM时维持正常血糖水平的葡萄糖输注速率（GIR），在上述三种饮食组中分别为6.2±0.9、8.9±0.9和9.7±0.4 mg·kg⁻¹·min⁻¹，而在以普通饲料喂养的对照组中为16.1±1.0 mg·kg⁻¹·min⁻¹。用鱼油中的长链ω-3脂肪酸替代多不饱和脂肪饮食中11%的脂肪酸可使胰岛素作用恢复正常（GIR为15.0±1.3 mg·kg⁻¹·min⁻¹）。在多不饱和脂肪饮食中用短链ω-3脂肪酸（α-亚麻酸，18:3 ω-3）进行类似替代则无效（GIR为9.9±0.5 mg·kg⁻¹·min⁻¹），但能完全预防饱和脂肪饮食诱导的胰岛素抵抗（GIR为16.0±1.5 mg·kg⁻¹·min⁻¹），且在肝脏和外周组织中均有效。骨骼肌中的胰岛素敏感性与平均肌肉甘油三酯蓄积呈负相关（比目鱼肌和红色股四头肌的相关系数分别为0.95和0.86；P均小于0.01）。此外，红色股四头肌中磷脂所含长链ω-3脂肪酸的百分比与该肌肉中的胰岛素作用高度相关（r = 0.97）。我们得出以下结论：1）高脂饮食中特定的脂肪酸及其所处的脂质环境决定大鼠的胰岛素敏感性；2）骨骼肌中胰岛素作用受损与甘油三酯蓄积有关，提示细胞内存在葡萄糖-脂肪酸循环；3）骨骼肌磷脂中的长链ω-3脂肪酸可能对有效的胰岛素作用至关重要。
