The effect of
sepsis on
neutral amino acid transport systems A, ASC, and L, was studied in incubated rat soleus (
SOL) muscles. We also examined the effects of plasma from septic rats and of varying concentrations of
insulin (10 to 10(5) microU/mL), added in vitro to incubated muscles, on system A
amino acid transport.
Sepsis was induced by cecal
ligation and
puncture (CLP) in rats weighing 40 to 60 g. Control rats were
sham-operated. System A activity was assessed by determining uptake of 2-(methylamino)isobutyrate (
MeAIB) 16 hours after CLP or
sham-operation. System ASC was studied by measuring uptake of
alpha-aminoisobutyric acid (AIB) in the presence of 25 mmol/L
MeAIB and 25 mmol/L 2-amino-2-norbornane
carboxylic acid (BCH) to inhibit uptake by systems A and L. System L activity was defined as
sodium-independent uptake of
cycloleucine.
MeAIB uptake was reduced by 28% in muscles of septic rats, while
amino acid transport by systems ASC and L was almost identical in muscles from control and septic rats. Addition of plasma from septic rats to incubated normal
SOL muscles inhibited
MeAIB uptake by 31%. Addition of
insulin to the incubation medium resulted in increased uptake of
MeAIB, both in nonseptic and septic muscle. The lowest
hormone concentration tested that significantly enhanced
MeAIB uptake in nonseptic muscle was 10(2) microU/mL and in septic muscle 10 microU/mL. The results suggest that
sepsis in rats specifically inhibits
amino acid transport system A and that reduced muscle
amino acid uptake may be caused by a circulating factor in
sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)