Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis
Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis
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DOI：
10.1152/ajpgi.00510.2003
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发表时间：
2005-06-01
影响因子：
4.5
通讯作者：
Sonaka, I
中科院分区：
文献类型：
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作者：
Nishitani, S;Takehana, K;Sonaka, I
众所周知，糖代谢受损是肝硬化患者的常见并发症。我们以前表明，亮氨酸，支链氨基酸（BCAA）的一种，促进葡萄糖摄取在无胰岛素的条件下，在离体骨骼肌从正常大鼠。本研究的目的是评估支链氨基酸对四氯化碳诱导的肝硬化大鼠模型（四氯化碳大鼠）的葡萄糖代谢的影响。口服葡萄糖耐量试验进行了BCAA处理的四氯化碳大鼠。在CCl4大鼠中，用亮氨酸或异亮氨酸而不是缬氨酸治疗，显著改善了葡萄糖耐量，其中异亮氨酸的效果大于亮氨酸的效果。葡萄糖摄取实验使用离体比目鱼肌从四氯化碳大鼠显示，亮氨酸和异亮氨酸，但不是缬氨酸，促进葡萄糖摄取在无胰岛素的条件下。为了阐明BCAA的降血糖作用的机制，我们收集了BCAA处理的CCl4大鼠的比目鱼肌，有或没有葡萄糖负荷。这些样品用于确定葡萄糖转运蛋白和糖原合酶（GS）活性的亚细胞位置。在没有葡萄糖负荷的情况下口服亮氨酸或异亮氨酸诱导GLUT4和GLUT1易位至质膜。GS活性仅在亮氨酸处理的大鼠中增强，并且被雷帕霉素（雷帕霉素的哺乳动物靶点抑制剂）完全抑制。总之，我们发现亮氨酸和异亮氨酸通过促进骨骼肌中葡萄糖的摄取来改善CCl4大鼠的葡萄糖代谢。这种效应是由于GLUT 4和GLUT 1的上调以及骨骼肌中GS的雷帕霉素依赖性激活的哺乳动物靶标而发生的。根据这些结果，我们认为支链氨基酸治疗可能对糖尿病患者的葡萄糖代谢有有益的影响。
It is well established that impaired glucose metabolism is a frequent complication in patients with hepatic cirrhosis. We previously showed that leucine, one of the branched-chain amino acids (BCAA), promotes glucose uptake under insulin-free conditions in isolated skeletal muscle from normal rats. The aim of the present study was to evaluate the effects of BCAA on glucose metabolism in a rat model of CCl4-induced cirrhosis (CCl4 rats). Oral glucose tolerance tests were performed on BCAA-treated CCl4 rats. In the CCl4 rats, treatment with leucine or isoleucine, but not valine, improved glucose tolerance significantly, with the effect of isoleucine being greater than the effect of leucine. Glucose uptake experiments using isolated soleus muscle from the CCl4 rats revealed that leucine and isoleucine, but not valine, promoted glucose uptake under insulin-free conditions. To clarify the mechanism of the blood glucose-lowering effects of BCAA, we collected soleus muscles from BCAA-treated CCl4 rats with or without a glucose load. These samples were used to determine the subcellular location of glucose transporter proteins and glycogen synthase (GS) activity. Oral administration of leucine or isoleucine without a glucose load induced GLUT4 and GLUT1 translocation to the plasma membrane. GS activity was augmented only in leucine-treated rats and was completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. In summary, we found that leucine and isoleucine improved glucose metabolism in CCl4 rats by promoting glucose uptake in skeletal muscle. This effect occurred as a result of upregulation of GLUT4 and GLUT1 and also by mammalian target of rapamycin-dependent activation of GS in skeletal muscle. From these results, we consider that BCAA treatment may have beneficial effects on glucose metabolism in cirrhotic patients.