The effect of insulin-like growth factor-1 on protein metabolism and hepatic response to endotoxemia in parenterally fed rats.
To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190-230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats.
Dickerson
R N
RN
University of Tennessee, Memphis.
Manzo
C B
CB
Charland
S L
SL
Settle
R G
RG
Stein
T P
TP
Kuhl
D A
DA
Rajter
J J
JJ
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004731:Endotoxins / Q000097:blood*; D002149:Energy Intake; D004926:Escherichia coli; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008762:Methylhistidines / Q000652:urine; D009584:Nitrogen / Q000008:administration & dosage / Q000378:metabolism; D010288:Parenteral Nutrition; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D008070:Lipopolysaccharides; D008762:Methylhistidines; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D003577:Cytochrome P-450 Enzyme System; D003404:Creatinine; D015660:7-Alkoxycoumarin O-Dealkylase; C028118:3-methylhistidine; D009584:Nitrogen