Insulin stimulates fatty acid transport by regulating expression of FAT/CD36 but not FABPpm
Insulin stimulates fatty acid transport by regulating expression of FAT/CD36 but not FABPpm
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DOI：
10.1152/ajpendo.00573.2003
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发表时间：
2004-10-01
影响因子：
5.1
通讯作者：
Bonen, A
中科院分区：
文献类型：
--
作者：
Chabowski, A;Coort, SLM;Bonen, A
由于胰岛素已被证明可以刺激骨骼肌和心肌细胞中的长链脂肪酸（LCFA）酯化，我们研究了胰岛素是否通过改变脂肪酸转运蛋白FAT/CD 36和FABPpm的表达和亚细胞分布来增加LCFA转运的速率。在心肌细胞中，胰岛素以时间和剂量依赖性方式非常迅速地增加FAT/CD 36蛋白的表达。在2小时内，胰岛素（10 nM）在60分钟后使心肌细胞FAT/CD 36蛋白增加25%，并在90 - 120分钟后达到最大值（+ 40 - 50%）。胰岛素（10（-12）至10（-7）M）与FAT/CD 36表达之间存在剂量依赖关系。FAT/CD 36蛋白的半数最大增加发生在0.5 × 10（-9）M胰岛素时，最大增加发生在10（-9）至10（-8）M胰岛素时（+40-50%）。在心肌细胞（+ 43%）和Langendorff灌注心脏（+ 32%）中，胰岛素诱导的FAT/CD 36蛋白增加相似。与FAT/CD 36相比，胰岛素不改变FABPpm蛋白在心肌细胞或灌注心脏中的表达。通过使用胰岛素信号传导途径的特异性抑制剂，表明胰岛素诱导的FAT/CD 36表达通过PI 3-激酶/Akt胰岛素信号传导途径发生。心肌细胞的亚细胞分级显示，胰岛素不仅增加了FAT/CD 36的表达，而且这种激素还将一些FAT/CD 36靶向质膜，同时降低了FAT/CD 36的细胞内贮库。在功能水平上，胰岛素诱导的FAT/CD 36蛋白增加导致棕榈酸转运到巨囊泡中的速率增加（+ 34%），这抵消了质膜FAT/CD 36的增加（+ 29%）。目前的研究表明，胰岛素通过PI 3-激酶/Akt胰岛素信号通路调节FAT/CD 36的蛋白表达，但不调节FABPpm。
Because insulin has been shown to stimulate long-chain fatty acid (LCFA) esterification in skeletal muscle and cardiac myocytes, we investigated whether insulin increased the rate of LCFA transport by altering the expression and the subcellular distribution of the fatty acid transporters FAT/CD36 and FABPpm. In cardiac myocytes, insulin very rapidly increased the expression of FAT/CD36 protein in a time- and dose-dependent manner. During a 2-h period, insulin ( 10 nM) increased cardiac myocyte FAT/CD36 protein by 25% after 60 min and attained a maximum after 90 - 120 min ( + 40 - 50%). There was a dose-dependent relationship between insulin ( 10(-12) to 10(-7) M) and FAT/CD36 expression. The half-maximal increase in FAT/CD36 protein occurred at 0.5 x 10(-9) M insulin, and the maximal increase occurred at 10(-9) to 10(-8) M insulin (+40 - 50%). There were similar insulin-induced increments in FAT/CD36 protein in cardiac myocytes ( + 43%) and in Langendorff-perfused hearts ( + 32%). In contrast to FAT/CD36, insulin did not alter the expression of FABPpm protein in either cardiac myocytes or the perfused heart. By use of specific inhibitors of insulin-signaling pathways, it was shown that insulin-induced expression of FAT/CD36 occurred via the PI 3-kinase/Akt insulin-signaling pathway. Subcellular fractionation of cardiac myocytes revealed that insulin not only increased the expression of FAT/CD36, but this hormone also targeted some of the FAT/CD36 to the plasma membrane while concomitantly lowering the intracellular depot of FAT/ CD36. At the functional level, the insulin-induced increase in FAT/ CD36 protein resulted in an increased rate of palmitate transport into giant vesicles ( + 34%), which paralleled the increase in plasmalemmal FAT/ CD36 ( + 29%). The present studies have shown that insulin regulates protein expression of FAT/ CD36, but not FABPpm, via the PI 3-kinase/Akt insulin-signaling pathway.