Effect of sepsis on amino acid transport system A and its response to insulin in incubated rat skeletal muscle.
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)
James
J H
JH
Department of Surgery, University of Cincinnati Medical Center, OH 45267-0558.
Hasselgren
P O
PO
Hummel
R P
RP
Warner
B W
BW
Fischer
J E
JE
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007328:Insulin; C017911:2-(methylamino)isobutyric acid