Decreased Uptake of Glucose by Human Forearm During Infusion of Leucine, Isoleucine, or Threonine

Competition between glucose and free fatty acids as metabolic fuels is supported by both in vitro and in vivo data, but whether amino acids can also compete with glucose as a source of energy in vivo remains to be established. To determine the effect of increased availability of an amino acid on whole-body glucose flux and glucose carbon uptake by the human forearm, five groups of overnight-fasted normal subjects were infused with either saline, leucine (at 0.5 or 1.0μmol · kg⁻¹ · min⁻¹), isoleucine (0.5 μmol · kg⁻¹ · min⁻¹), or threonine (0.5 μmol · kg⁻¹ · min⁻¹). Plasma glucose concentrations and glucose flux decreased similarly in all groups. No significant changes in forearm output of leucine carbon, isoleucine carbon, or threonine were seen during saline infusion. In contrast, during leucine infusion there was a dose-dependent increase (r = .86, P < .001) in leucine carbon uptake with increased arterial leucine and a-ketoisocaproate concentrations. During infusions of isoleucine and threonine, increases (P < .05) in isoleucine carbon uptake and threonine uptake, respectively, were observed. Glucose uptake by forearm tissues did not change during the saline infusion, but it decreased (P < .05) in all four groups receiving an amino acid infusion. Changes in leucine carbon uptake were strongly correlated (r = −.76, P < .001) with changes in glucose uptake. Therefore, amino acids affect glucose uptake in human forearm tissue and presumably compete as oxidative fuels.