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Analysis of the hypoglycemic effect of branched-chain amino acids and possible contribution of branched-chain amino acids to a treatment for diabetes

支链氨基酸的降血糖作用分析以及支链氨基酸对糖尿病治疗的可能贡献

基本信息

批准号：
17580104
负责人：
YOSHIZAWA Fumiaki
金额：
$ 2.24万
依托单位：
Utsunomiya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Recent studies have demonstrated that a branched-chain amino acids (BCAAs) mixture decreases the plasma glucose levels in vivo. However, it is not known if this reflects glucose metabolism caused by leucine, isoleucine or valine, and the mechanism of the effects of each of the BCAAs is not understood. This study was designed to examine the effects of BCAAs on the plasma glucose levels in rats. We found that among the BCAAs, leucine and isoleucine increase glucose uptake in an insulin-independent manner, with the effect of isoleucine being greater than that seen for leucine. We also have shown that oral administration of isoleucine, which does not stimulate insulin secretion, has a potent hypoglycemic effect and increases glucose uptake in muscle in contrast to the lack of this effect after an oral administration of leucine in rats. The alternations in muscle glucose metabolism by isoleucine were caused in the absence of increases in AMP-activated protein kinase activity, which has been thought to be associated with an insulin-independent glucose uptake. This suggests that there are other as-yet unknown signaling pathways involved in this phenomenon. We also assessed whether oral administration of BCAAs has a potent hypoglycemic effect in diabetic rats. After being fasted for 18 hours, the type 2 diabetic rats (GK rats) were administered 135 mg/ 100 g body weight leucine or isoleucine by oral gavage and were fed the 20% casein diet immediately after oral administration of amino acid. Blood samples were collected by tail bleeding at 1 h after feeding began, and the plasma glucose levels were measured. Oral administration of leucine or isoleucine decreased plasma glucose compared to saline administered control. These results suggested that leucine or isoleucine could be an important therapeutic resource among diabetics to avoid the characteristic hyperglycemia of this disease.

最近的研究表明，支链氨基酸（BCAAs）混合物降低体内血糖水平。然而，目前尚不清楚这是否反映了亮氨酸、异亮氨酸或缬氨酸引起的葡萄糖代谢，也不清楚每种支链氨基酸的作用机制。本研究旨在研究支链氨基酸对大鼠血糖水平的影响。我们发现，在支链氨基酸中，亮氨酸和异亮氨酸以不依赖胰岛素的方式增加葡萄糖摄取，其中异亮氨酸的作用大于亮氨酸。我们还表明，口服不刺激胰岛素分泌的异亮氨酸具有有效的降血糖作用，并增加肌肉中的葡萄糖摄取，而在大鼠中口服亮氨酸后缺乏这种作用。在肌肉葡萄糖代谢的异亮氨酸的变化引起的AMP激活的蛋白激酶活性，这被认为是与胰岛素非依赖性的葡萄糖摄取增加的情况下。这表明，还有其他未知的信号通路参与了这一现象。我们还评估了口服支链氨基酸是否对糖尿病大鼠具有有效的降血糖作用。在禁食18小时后，通过经口管饲法向2型糖尿病大鼠（GK大鼠）施用135 mg/ 100 g体重的亮氨酸或异亮氨酸，并在经口施用氨基酸后立即饲喂20%酪蛋白饮食。在喂食开始后1h通过尾部放血收集血液样品，并测量血浆葡萄糖水平。与施用生理盐水的对照相比，口服施用亮氨酸或异亮氨酸降低血浆葡萄糖。这些结果表明，亮氨酸或异亮氨酸可能是一个重要的治疗资源，在糖尿病患者，以避免这种疾病的特征性高血糖。