Recent investigations have revealed that the energy excess derived from amino acids activates mTOR and/or S6K1, which leads to insulin resistance (20, 21, 35). However, the single amino acid isoleucine decreases blood glucose through a si- multaneous increase in glucose utilization that actually im- proves glucose metabolism and energy states of both the muscle and liver (Fig. 8). Although the molecular basis of these findings remains to be determined, elucidation of the associa- tions related to these factors when using isoleucine may pro- vide new insights into the role of amino acids on metabolic disorders related to insulin resistance.
In conclusion, our study revealed that isoleucine lowers blood glucose levels by both stimulation of the muscle glucose uptake and an increase in glucose oxidation within the whole body without significant elevation of plasma insulin levels. Our study also showed that isoleucine reduces hepatic glucose production in vitro and the expression and activity of hepatic gluconeogenic enzymes both in vitro and in vivo. By achieving a better understanding of the mechanism of isoleucine’s activ- ity, this may potentially provide important information relevant to the effects of amino acids on glucose metabolism.