Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity
Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity
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DOI：
10.1093/jn/135.9.2103
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发表时间：
2005-09-01
影响因子：
4.2
通讯作者：
Yoshizawa, F
中科院分区：
文献类型：
--
作者：
Doi, M;Yamaoka, I;Yoshizawa, F
亮氨酸和异亮氨酸在体外刺激骨骼肌细胞的胰岛素非依赖性葡萄糖摄取。在这项研究中，我们研究了亮氨酸和异亮氨酸对食物剥夺大鼠血糖和体内骨骼肌葡萄糖代谢的影响。此外，我们研究了能量传感器5 '-AMP激活的蛋白激酶（AMPK）可能参与骨骼肌葡萄糖摄取的调节，这与胰岛素无关，也参与亮氨酸或异亮氨酸刺激的葡萄糖摄取。口服异亮氨酸，而不是亮氨酸，显著降低血糖浓度。静脉推注2-[1，2-H-3]-脱氧葡萄糖（2-[H-3]DG）以计算葡萄糖摄取。骨骼肌中的葡萄糖摄取在亮氨酸给药后没有差异，但异亮氨酸给药大鼠肌肉中的葡萄糖摄取比对照组高73%，表明异亮氨酸增加体内骨骼肌葡萄糖摄取。相反，在骨骼肌中，与对照组相比，亮氨酸而不是异亮氨酸的给药显著增加了[U-C-14]葡萄糖掺入糖原。骨骼肌中AMPK α 1活性不受亮氨酸或异亮氨酸给药的影响。然而，异亮氨酸，而不是亮氨酸，显着降低AMPK α 2活性。AMPK α 2活性的降低被认为是由于AMP含量和AMP：ATP比率的降低，这与异亮氨酸给药有关。这是首次报道异亮氨酸在体内刺激大鼠骨骼肌中的葡萄糖摄取，这些结果表明，在大鼠中施用异亮氨酸时发生的血糖降低和骨骼肌葡萄糖摄取增加之间可能存在关系。异亮氨酸引起的葡萄糖代谢的改变可能会导致骨骼肌中AMP激活的蛋白激酶活性增加的情况下ATP的可用性改善。
Leucine and isoleucine were shown to stimulate insulin-independent glucose uptake in skeletal muscle cells in vitro. In this study, we examined the effects of leucine and isoleucine on blood glucose in food-deprived rats and on glucose metabolism in skeletal muscle in vivo. Furthermore, we investigated the possible involvement of the energy sensor, 5'-AMP-activated protein kinase (AMPK), in the modulation of glucose uptake in skeletal muscle, which is independent of insulin, and also in leucine- or isoleucine-stimulated glucose uptake. Oral administration of isoleucine, but not leucine, significantly decreased the plasma glucose concentration. An i.v. bolus of 2-[1,2-H-3]-deoxyglucose (2-[H-3]DG) was administered to calculate glucose uptake. Glucose uptake in the skeletal muscle did not differ after leucine administration, but glucose uptake in the muscles of rats administered isoleucine was 73% greater than in controls, suggesting that isoleucine increases skeletal muscle glucose uptake in vivo. On the contrary, in the skeletal muscles, administration of leucine but not isoleucine significantly increased [U-C-14]glucose incorporation into glycogen compared with controls. AMPK alpha 1 activity in skeletal muscle was not affected by leucine or isoleucine administration. However, isoleucine, but not leucine, significantly decreased AMPK alpha 2 activity. The decrease in AMPK alpha 2 activity was thought to be due to decreases in AMP content and the AMP:ATP ratio, which were related to the isoleucine administration. This is the first report of isoleucine stimulating glucose uptake in rat skeletal muscle in vivo, and these results indicate that there might be a relation between the reduction in blood glucose and the increase in skeletal muscle glucose uptake that occur with isoleucine administration in rats. The alterations in glucose metabolism caused by isoleucine may result in an improvement of the availability of ATP in the absence of increases in AMP-activated protein kinase activity in skeletal muscle.