EFFECT OF HUMAN INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 ON THE HALF-LIFE AND ACTION OF ADMINISTERED INSULIN-LIKE GROWTH FACTOR-I IN RATS

We have determined the effect of human insulin-like growth factor-binding protein-1 (hIGFBP-1) on the circulating half-life (t1/2) of human insulin-like growth factor-I (hIGF-1) and on hIGF-I-stimulated 2-deoxy-glucose uptake in tissues of the cannulated conscious rat. The levels of hIGF-I in rat serum were measured by radioimmunoassay. The assay was carried out in the presence of partially purified rat IGF to remove interference from any IGFBPs not removed by acid-ethanol extraction. An intravenous bolus of 12.5 mug hIGF-I, given to 12-h fasted rats, disappeared from the circulation in a double exponential fashion with an initial t1/2 of 1-2 +/- 0.2 min (n = 8), which increased to 5.3 +/- 0.9 min when 100 mug hIGFBP-1 was co-administered (n = 5; P < 0.001). The second phase of disappearance of hIGF-I indicated an apparent t1/2 of 35.7 +/- 5.6 min which was not significantly altered by the co-infusion of hIGFBP-1. Circulating hIGFBP-1, measured with a primate-specific radioimmunoassay, disappeared in a single exponential fashion with a t1/2 of 8.8 +/- 0.7 min. A tracer amount of 2-deoxy-[1-H-3]glucose was administered intravenously at the same time as the peptide(s) and the rate of tissue uptake and phosphorylation of 2-deoxy[1-H-3]glucose determined. Compared with a control group (n = 4), hIGF-I significantly stimulated hexose uptake into heart, soleus and red quadriceps muscles and hIGFBP-1 partially reversed this effect. We propose that the insulin-like activity of unbound IGFs in the circulation may be regulated in vivo by fluctuating endogenous IGFBP-1 levels, so that the IGFs, along with IGFBP-1, may represent a dynamic glucoregulatory system.