In addition to a possible role of BCAA in modifying glucose homeostasis, BCAA have a well-described positive role in maintaining muscle protein turnover. Therefore, any information about a causal role of BCAA in altering insulin sensitivity of glucose metabolism in humans is of both physiological and clinical importance. An experimental approach where the insulin sensitivity is evaluated in the presence of acute exposure to increased L-694,247 plasma BCAA concentrations can directly address the short-term LOE 908 hydrochloride effects of increased plasma BCAA concentrations on hindering insulin sensitivity. The role of increased plasma BCAA in modifying insulin sensitivity has been a topic of heavy debate. This is the first study to directly evaluate the effects of short-term exposure to increased BCAA levels on plasma glucose turnover in humans. The primary end-point of the study was the change in whole-body glucose disposal, reflecting primarily insulin sensitivity of glucose metabolism in muscle. Our results show that short-term exposure to increased plasma BCAA concentrations does not modify the insulin sensitivity of glucose metabolism in healthy, young humans. By design, the BCAA infusion resulted in more than 2.5-fold increase in the concentration of plasma BCAA for a period of 6 hours, and at levels above those observed in either obesity or the fed state associated with the ingestion of high protein meal. We found that increasing the plasma insulin concentrations completely suppressed the EGP both in the control and BCAA groups. These findings agree with previous findings describing the response of EGP to insulin in association with the infusion of a mixture of amino acids that increased the plasma concentration of total amino acids. It is recognized, however, that the present study, as well as the previous studies, may be limited in their ability to distinguish differences in EGP in the presence of increased plasma amino acids when plasma insulin concentrations are raised at levels that result in complete suppression of EGP. The product of EGP and plasma insulin concentration, which was used as an additional measure in evaluating hepatic insulin sensitivity in the basal period and at a time when plasma insulin levels were relatively low in both the control and BCAA groups, indicated no differences in hepatic insulin sensitivity between the two groups. Therefore, the overall findings of the present studies suggest that short-term exposure to increased plasma BCAA concentrations does not impair insulin action in the liver in healthy young adults.