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

最近的研究表明，支链氨基酸（BCAAs）混合物可以降低体内血浆葡萄糖水平。然而，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尚不清楚，并且每种支链氨基酸的作用机制尚不清楚。本研究旨在探讨支链氨基酸对大鼠血浆葡萄糖水平的影响。我们发现，在支链氨基酸中，亮氨酸和异亮氨酸以胰岛素不依赖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，口服异亮氨酸不刺激胰岛素分泌，但具有有效的降糖作用，并增加肌肉中葡萄糖的摄取，而口服亮氨酸在大鼠中没有这种作用。异亮氨酸引起的肌肉葡萄糖代谢的改变是在amp激活的蛋白激酶活性没有增加的情况下引起的，这被认为与胰岛素不依赖型葡萄糖摄取有关。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有有效的降糖作用。禁食18小时后，2型糖尿病大鼠（GK大鼠）灌胃135 mg/ 100 g体重的亮氨酸或异亮氨酸，并在口服氨基酸后立即饲喂20%酪蛋白的日粮。饲喂后1 h尾出血采血，测定血浆葡萄糖水平。与生理盐水对照组相比，口服亮氨酸或异亮氨酸可降低血糖。这些结果提示亮氨酸或异亮氨酸可能是糖尿病患者避免特征性高血糖的重要治疗资源。

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.