Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36
Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36
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DOI：
10.2337/diabetes.51.10.3113
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Glatz, JFC
中科院分区：
文献类型：
--
作者：
Luiken, JJFP;Koonen, DPY;Glatz, JFC
细胞内脂肪酸转位酶 (FAT/CD36) 库、长链脂肪酸 (FA) 的空气 88 kDa 膜转运蛋白以及胰岛素诱导转位事件的能力的存在促使我们研究胰岛素对心脏细胞摄取 FA 的直接影响。胰岛素（0.1 nmol/l 及更高）可使离体大鼠心肌细胞对 FA 的摄取增加 1.5 倍。这种胰岛素诱导的 FA 摄取增加被根皮素、磺基-N-琥珀酰亚胺基棕榈酸酯 (SSP) 和渥曼青霉素完全阻断，表明 FAT/CD36 的参与以及对磷脂酰肌醇-3 (PI-3) 激酶激活的依赖性。胰岛素刺激的心肌细胞的亚细胞分离显示，肌膜 FAT/CD36 增加了 1.5 倍，细胞内 FAT/CD36 减少了 62%，同时 GLUT4 的亚细胞分布也发生了平行变化。4 Hz 电刺激诱导细胞收缩，增强了细胞 FA 摄取 1.6 倍，与 PI-3 激酶无关。向 4 Hz 刺激的细胞中添加胰岛素进一步刺激 FA 摄取达到 2.3 倍，这表明至少有两个功能独立的细胞内 FAT/CD36 池，一个由胰岛素募集，另一个由收缩动员。总之，我们证明了胰岛素在心脏 FA 利用中的新作用。胰岛素诱导的 FAT/CD36 易位功能障碍可能与 2 型糖尿病心肌病的发生有关。
The existence of an intracellular pool of fatty acid translocase (FAT/CD36), air 88-kDa membrane transporter for long-chain fatty acids (FAs), and the ability of insulin to induce translocation events prompted us to investigate the direct effects of insulin on cellular uptake of FA by the heart. Insulin (0.1 nmol/l and higher) increased FA uptake by isolated rat cardiac myocytes by 1.5-fold. This insulin-induced increase in FA uptake was completely blocked by phloretin, sulfo-N-succinimidylpalmitate (SSP), and wortmannin, indicating the involvement of FAT/CD36 and the dependence on phosphatidylinositol-3 (PI-3) kinase activation. Subcellular fractionation of insulin-stimulated cardiac myocytes demonstrated a 1.5-fold increase in sarcolemmal FAT/CD36 and a 62% decrease in intracellular FAT/ CD36 with parallel changes in subcellular distribution of GLUT4.. Induction of cellular contractions upon electrostimulation at 4 Hz enhanced cellular FA uptake 1.6-fold, independent of PI-3 kinase. The addition of insulin to 4 Hz-stimulated cells further stimulated FA uptake to 2.3-fold, indicating that there are at least two functionally independent intracellular FAT/CD36 pools, one recruited by insulin and the other mobilized by contractions. In conclusion, we have demonstrated a novel role of insulin in cardiac FA.utilization. Malfunctioning of insulin-induced FAT/CD36 translocation may be involved in the development of type 2 diabetic cardiomyopathies.