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

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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.