O-glycosylation delays the clearance of human IGF-binding protein-6 from the circulation

The actions of insulin-like growth factors (IGF-I and IGF-II) are modulated by a family of six structurally related, high-affinity binding proteins (IGFBPs 1-6). IGFBP-6, an O-linked glycoprotein, preferentially binds IGF-II and inhibits its actions. The aim of this study was to investigate whether...

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Bibliographic Details
Published in:European journal of endocrinology 2000-05, Vol.142 (5), p.512-516
Main Authors: MARINARO, J. A, CASLEY, D. J, BACH, L. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
General pharmacology
Glycosylation
Half-Life
Humans
Injections, Intravenous
Insulin-Like Growth Factor Binding Protein 6 - administration & dosage
Insulin-Like Growth Factor Binding Protein 6 - metabolism
Insulin-Like Growth Factor Binding Protein 6 - pharmacokinetics
Iodine Radioisotopes
Male
Medical sciences
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Recombinant Proteins - administration & dosage
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacokinetics
Tissue Distribution
Tropical medicine
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Summary:The actions of insulin-like growth factors (IGF-I and IGF-II) are modulated by a family of six structurally related, high-affinity binding proteins (IGFBPs 1-6). IGFBP-6, an O-linked glycoprotein, preferentially binds IGF-II and inhibits its actions. The aim of this study was to investigate whether O-glycosylation modulates the pharmacokinetics of IGFBP-6. The pharmacokinetic profiles of (125)I-labelled glycosylated (g) and non-glycosylated (n-g) recombinant human IGFBP-6 were studied following intravenous bolus administration in anaesthetised rats. The redistribution half-life of gIGFBP-6 was 2.3-fold greater than that of n-gIGFBP-6 (14.4+/- 1.2 vs 6.3+/-1.5 min, P=0. 006). The elimination half-life of gIGFBP-6 was 21-fold greater than that of n-gIGFBP-6 (584.2+/-130.2 vs 28.0+/-4.2 min, P=0.019). The effect of O-glycosylation on IGFBP-6 pharmacokinetics was not due to inhibition of intravascular proteolysis. Radioactivity was found in stomach, kidneys, lung, spleen, heart and liver but not brain 4h after injection of g or n-gIGFBP-6. O-glycosylation delays the clearance of IGFBP-6 from the circulation and may therefore contribute to its role as a circulating inhibitor of IGF-II actions.
ISSN:0804-4643
1479-683X
DOI:10.1530/eje.0.1420512