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

Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia.

OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

This article has been cited by other articles:

				I. Khalaila, J. Peter-Katalinic, C. Tsang, C. M. Radcliffe, E. D. Aflalo, D. J. Harvey, R. A. Dwek, P. M. Rudd, and A. Sagi Structural characterization of the N-glycan moiety and site of glycosylation in vitellogenin from the decapod crustacean Cherax quadricarinatus Glycobiology, September 1, 2004; 14(9): 767 - 774. [Abstract] [Full Text] [PDF]

				G. Bienvenu, D. Seurin, P. Grellier, P. Froment, M. Baudrimont, P. Monget, Y. Le Bouc, and S. Babajko Insulin-Like Growth Factor Binding Protein-6 Transgenic Mice: Postnatal Growth, Brain Development, and Reproduction Abnormalities Endocrinology, May 1, 2004; 145(5): 2412 - 2420. [Abstract] [Full Text] [PDF]