Turcotte L P, Swenberger J R, Zavitz Tucker M, Yee A J
Department of Kinesiology and University of Southern California Diabetes Center, University of Southern California, 3560 Watt Way, PED 107, Los Angeles, CA 90089, USA.
Diabetes. 2001 Jun;50(6):1389-96. doi: 10.2337/diabetes.50.6.1389.
Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determine whether FA uptake and disposal are altered in insulin-resistant muscle, we measured palmitate uptake, oxidation, and incorporation into di- and triglycerides in isolated rat hindquarters, as well as muscle plasma membrane fatty acid-binding protein (FABP(PM)) content of lean (n = 16, fa/+) and obese (n = 15, fa/fa) Zucker rats (12 weeks of age). Hindquarters were perfused with 7 mmol/l glucose, 1,000 micromol/l albumin-bound palmitate, and albumin-bound [1-(14)C]palmitate at rest (no insulin). Glucose uptake was 42% lower in the obese than in the lean rats and indicated the presence of muscle insulin resistance. Fractional and total rates of palmitate uptake were 42 and 74% higher in the obese than in the lean rats and were associated with higher muscle FABP(PM) content (r(2) = 0.69, P < 0.05). The percentage of palmitate oxidized was not significantly different between groups. FA disposal to storage was altered according to fiber type. When compared with lean rats, the rate of triglyceride synthesis in red muscle was 158% higher in obese rats, and the rate of palmitate incorporation into diglycerides in white muscle was 93% higher in obese rats. Pre- and postperfusion muscle triglyceride levels were higher in both red and white muscles of the obese rats. These results show that increased FA uptake and altered FA disposal to storage may contribute to the development of muscle insulin resistance in obese Zucker rats.
在遗传性肥胖的 Zucker 大鼠中，肌肉脂肪酸（FA）代谢改变可能导致肌肉胰岛素抵抗的出现。为了确定胰岛素抵抗肌肉中 FA 的摄取和代谢是否发生改变，我们测量了分离的大鼠后肢中棕榈酸的摄取、氧化以及其掺入甘油二酯和甘油三酯的情况，同时还测量了 12 周龄的瘦型（n = 16，fa/+）和肥胖型（n = 15，fa/fa）Zucker 大鼠肌肉质膜脂肪酸结合蛋白（FABP(PM)）的含量。后肢在静息状态（无胰岛素）下用 7 mmol/l 葡萄糖、1000 μmol/l 白蛋白结合的棕榈酸以及白蛋白结合的 [1-(14)C]棕榈酸进行灌注。肥胖大鼠的葡萄糖摄取量比瘦型大鼠低 42%，表明存在肌肉胰岛素抵抗。肥胖大鼠中棕榈酸的分数摄取率和总摄取率分别比瘦型大鼠高 42%和 74%，且与更高的肌肉 FABP(PM) 含量相关（r(2) = 0.69，P < 0.05）。两组之间棕榈酸氧化的百分比没有显著差异。FA 向储存的代谢根据纤维类型而改变。与瘦型大鼠相比，肥胖大鼠红色肌肉中甘油三酯合成速率高 158%，白色肌肉中棕榈酸掺入甘油二酯的速率高 93%。肥胖大鼠红色和白色肌肉灌注前和灌注后的肌肉甘油三酯水平均较高。这些结果表明，FA 摄取增加和 FA 向储存的代谢改变可能导致肥胖 Zucker 大鼠肌肉胰岛素抵抗的发生。
