It has been suggested that
leucine and
alpha-ketoisocaproic acid (KIA) stimulate
protein synthesis and reduce
protein breakdown and may be useful in the treatment of muscle catabolism during
sepsis. However, whether
leucine and KIA regulate
protein turnover in septic skeletal muscle is not known. In this study, intact muscles from untreated normal rats or from rats subjected to cecal
ligation and
puncture were incubated in the presence of
leucine or KIA. In normal muscle,
leucine stimulated
protein synthesis and reduced protein degradation, while KIA decreased
protein breakdown. In septic
muscle, protein synthesis was also stimulated by
leucine, but only at a concentration higher than that needed to affect
protein synthesis in normal muscle.
Protein breakdown in septic muscle was unaffected by
leucine and KIA even at an extracellular concentration as high as 5 mmol/L. Since other experiments showed that the intracellular concentration of
leucine was not different in incubated normal and septic muscles, these results suggest that
sepsis induces changes in skeletal muscle
protein turnover that are resistant to the effects of
leucine.