TY - JOUR
T1 - Effect of sepsis on amino acid transport system A and its response to insulin in incubated rat skeletal muscle
AU - James, J. Howard
AU - Hasselgren, Per Olof
AU - Hummel, Robert P.
AU - Warner, Brad W.
AU - Fischer, Josef E.
N1 - Funding Information:
From the Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH. Supported in part by National Institutes of Health Grant No. I ROI DK 37908-01. Dr Hummel was a recipient of the John W&in Fellowship, University of Cincinnati College of Medicine, Department of Surgery. Address reprint requests to Josef E. Fischer, MD, Department of Surgery, University of Cincinnati Medical Center, 231 Bethesda Ave (ML#558). Cincinnati, OH 4.5267-0558. o 1990 by W.B. Saunders Company. 00260495/90/3904-0001$3.00/0
PY - 1990/4
Y1 - 1990/4
N2 - 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 105 μU/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 α-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 102 μU/mL and in septic muscle 10 μU/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. Physiological concentrations of insulin stimulate system A amino acid transport in incubated skeletal muscle of both nonseptic and septic rats.
AB - 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 105 μU/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 α-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 102 μU/mL and in septic muscle 10 μU/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. Physiological concentrations of insulin stimulate system A amino acid transport in incubated skeletal muscle of both nonseptic and septic rats.
UR - http://www.scopus.com/inward/record.url?scp=0025217792&partnerID=8YFLogxK
U2 - 10.1016/0026-0495(90)90245-8
DO - 10.1016/0026-0495(90)90245-8
M3 - Article
C2 - 2182970
AN - SCOPUS:0025217792
SN - 0026-0495
VL - 39
SP - 335
EP - 340
JO - Metabolism
JF - Metabolism
IS - 4
ER -