Effects of chronic renal failure on plasma clearance of insulin
-like growth factor-i, des(1-3)igf-i and lr3igf-i.
Gillespie, C. M., S. J. Hazel, P. E. Walton, A. A. Martin.
Cooperative Research Centre for Tissue Growth and Repair at the
Child Health Research Institute, North Adelaide, South Australia,
Australia 5006, and CSIRO Division of Human Nutrition, Adelaide,
South Australia
APStracts 3:0117E, 1996.
Using a rat model of chronic renal failure (CRF) we examined IGF-I
clearance, degradation, organ distribution and IGF binding profiles
in plasma. The effects of IGFBPs on IGF clearance and degradation in
CRF were studied utilising the IGF-I analogs des(1-3)IGF-I and
LR3IGF-I, which bind poorly to IGF binding proteins (IGFBPs). While
total clearance of IGF-I was not significantly altered in CRF, half
-life and area under the curve were increased in the rapid
distribution phase, and reduced in the slow elimination phase. Total
clearance of LR3IGF-I was significantly increased. Reduced binding of
IGF-I in the 150 kDa complex and increased binding to smaller
molecular weight IGFBPs were observed in CRF. Increased degradation
of both IGF-I and LR3IGF-I was associated with reduced IGF binding in
the 150kDa complex. The results suggest that the accumulation of
lower molecular weight IGFBPs with reduced IGF binding in the 150 kDa
complex, associated with increased degradation of peptide may
explain, at least in part, the reduced bioactivity of IGF-I observed
in CRF.
Received 5 February 1996; accepted in final form 4 June 1996.
APS Manuscript Number E72-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96