Insulin-like growth factor-binding protein-1 modulates blood glucose levels

We have determined the consequences of insulin-like growth factor-binding protein-1 (IGFBP-1) administration alone and in combination with insulin-like growth factor-I (IGF-I). Human recombinant IGF-I, infused as a bolus into male Wistar rats, induced a fall in plasma glucose to 72 +/- 3% of baseline 15 min after injection. Co-infusion of equimolar concentrations of human IGFBP-1 abolished the IGF-I-induced fall (P less than 0.001). Injection of IGFBP-1 alone caused a rise in plasma glucose levels (P less than 0.002). The half life of human IGFBP-1, measured using a primate-specific RIA, was 12.5 +/- 0.7 min and was not influenced by the co-infusion of IGF-I. This study demonstrates that, in the rat, human IGFBP-1 blocks the hypoglycemic response to intravenous IGF-I and increases blood glucose levels when administered alone. Since IGFBP-1 concentrations are dependent on metabolic status, we suggest that fluctuating IGFBP-1 levels might modulate the hypoglycemic activity of unbound IGFs in the circulation.