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ABSTRACT We have determined the effect of human insulin-like growth factor-binding protein-1 (hIGFBP-1) on the circulating half-life (t½) of human insulin-like growth factor-I (hIGF-I) and on hIGF-I-stimulated 2-deoxyglucose 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 μg hIGF-I, given to 12-h fasted rats, disappeared from the circulation in a double exponential fashion with an initial t½ of 1·2±0·2 min (n = 8), which increased to 5·3 ±0·9 min when 100 μg hIGFBP-1 was co-administered (n = 5; P <0·001). The second phase of disappearance of hIGF-I indicated an apparent t½ 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 t½ of 8·8±0·7 min. A tracer amount of 2-deoxy-[1-3H]glucose was administered intravenously at the same time as the peptide(s) and the rate of tissue uptake and phosphorylation of 2-deoxy-[1-3H]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. Journal of Endocrinology (1993) 136, 253–260