Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis
Hypoglycemic effect of isoleucine involves increased muscle glucose uptake and whole body glucose oxidation and decreased hepatic gluconeogenesis
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DOI：
10.1152/ajpendo.00609.2006
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发表时间：
2007-06-01
影响因子：
5.1
通讯作者：
Yoshizawa, Fumiaki
中科院分区：
文献类型：
--
作者：
Doi, Masako;Yamaoka, Ippei;Yoshizawa, Fumiaki
异亮氨酸是一种支链氨基酸，在改善葡萄糖代谢方面起着重要作用，如体外胰岛素非依赖性葡萄糖摄取增加所证明的。本研究评估了异亮氨酸对禁食大鼠葡萄糖摄取和氧化的影响以及对体内和体外胚胎发生的影响。与对照组相比，给药后60 min，口服异亮氨酸可使血糖水平降低20%，肌肉葡萄糖摄取显著增加71%，而血浆胰岛素水平无显著升高。此外，与对照组相比，异亮氨酸给药大鼠中[ U-C-14]葡萄糖的（CO2）-C-14呼气排泄增加了19%。同时，异亮氨酸降低AMP在肝脏中的水平，但不影响肝糖原合成。在无胰岛素条件下，当丙氨酸用作离体肝细胞中的生糖底物时，异亮氨酸显著抑制葡萄糖产生。异亮氨酸的这种抑制作用也与磷酸烯醇式丙酮酸羧激酶和葡萄糖-6-磷酸酶（G6 β）的mRNA水平下降以及分离的肝细胞中G6 β活性降低有关。这些发现表明，肝脏中的糖原合成减少，沿着肌肉中葡萄糖摄取增加，也参与了异亮氨酸的降血糖作用。总之，异亮氨酸给药刺激肌肉中的葡萄糖摄取和全身葡萄糖氧化，此外还抑制肝脏中的葡萄糖生成，从而导致大鼠的降血糖作用。
Isoleucine, a branched chain amino acid, plays an important role in the improvement of glucose metabolism as evidenced by the increase of insulin- independent glucose uptake in vitro. This study evaluated the effect of isoleucine on glucose uptake and oxidation in fasted rats and on gluconeogenesis in vivo and in vitro. Oral administration of isoleucine decreased the plasma glucose level by 20% and significantly increased muscle glucose uptake by 71% without significant elevation of the plasma insulin level compared with controls at 60 min after administration. Furthermore, expiratory excretion of (CO2)-C-14 from [ U-C-14] glucose in isoleucine- administered rats was increased by 19% compared with controls. Meanwhile, isoleucine decreased AMP levels in the liver but did not affect hepatic glycogen synthesis. Under insulin- free conditions, isoleucine significantly inhibited glucose production when alanine was used as a glucogenic substrate in isolated hepatocytes. This inhibition by isoleucine was also associated with a decline in mRNA levels for phosphoenolpyruvate carboxykinase and glucose-6-phosphatase ( G6Pase) and a decreased activity of G6Pase in isolated hepatocytes. These findings suggest that a reduction of gluconeogenesis in liver, along with an increase of glucose uptake in the muscle, is also involved in the hypoglycemic effect of isoleucine. In conclusion, isoleucine administration stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to the hypoglycemic effect in rats.