Inhibited muscle amino acid uptake in sepsis.
Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis.
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000378:metabolism*; D001692:Biological Transport; D002432:Cecum / Q000601:surgery; D003470:Culture Media; D003964:Diaphragm / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D066298:In Vitro Techniques; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011677:Punctures; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D003470:Culture Media; D004731:Endotoxins