Alterations in hepatic production and peripheral clearance of igf-i
after endotoxin.
Fan, Jie, Daniel Char, Alice J. Kolasa, Wansong Pan, Subir R. Maitra,
Clifford S. Patlak, Zoltan Spolarics, Marie C. Gelato, Charles H.
Lang.
Department of Surgery, Department of Medicine/Division of
Endocrinology, and Department of Emergency Medicine at the State
University of New York at Stony Brook, Stony Brook, NY, Department of
Anatomy, Cell Biology and Injury Sciences, University of Medicine and
Dentistry of New Jersey
APStracts 2:0029E, 1995.
Lipopolysaccharide (LPS) produces a rapid and sustained reduction in
the circulating concentration of IGF-I which may be responsible, in
part, for the alterations in protein metabolism observed in these
animals. The purpose of the present study was to determine whether
this drop was due to a decreased hepatic production of IGF-I and/or
an increased clearance of the peptide from the blood. Four hours
after IV injection of LPS the plasma IGF-I concentration was
decreased 50%. IGF-I release by in situ perfused livers from control
rats was constant throughout the 60-min perfusion period and averaged
111 +/- 3 ng/min. In contrast, hepatic IGF-I output was decreased 46%
by in vivo LPS. In contrast, livers from LPS-injected rats released
more IGF binding proteins-1, -2 and -4, than control livers. Hepatic
cell isolation indicated that LPS decreased the IGF-I content in
Kupffer and parenchymal cells, but not endothelial cells, by _45%.
Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated
that the half-life for whole-body clearance of 125I-IGF-I from the
circulation was not altered by LPS. However, LPS increased 125I-IGF-I
uptake by spleen, liver, lung and kidney, while decreasing uptake by
the pancreas and the gastrointestinal tract. These results indicate
that the LPS-induced decrease in blood IGF-I concentration is
primarily due to a reduction in hepatic production, not a change in
whole-body peptide clearance, and that a decreased production by both
parenchymal and Kupffer cells contributes to this alteration.
Received 8 November 1994; accepted in final form 14 February
1995.
APS Manuscript Number E463-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.