RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 (RHIGFBP-3) - EFFECTS ON THE GLYCEMIC AND GROWTH-PROMOTING ACTIVITIES OF RHIGF-1 IN THE RAT

The effects of IGFBPs on IGF-1 bioactivity in vivo remain largely unkn own. We have tested the ability of rhIGFBP-3, made in 293 cells or CHO cells, to affect the glycemic and anabolic activities of co-administe red rhIGF-1. For glycemic studies female dw/dw rats were anesthetized, a jugular catheter inserted, basal blood samples taken and i.v. injec tions given of rhIGF-1 (0.25 mg/kg), rhIGFBP-3 (0.50 mg/kg), or rhIGF- 1 plus rhIGFBP-3 (0.25 plus 0.50 mg/kg, respectively). The blood gluco se (20 min later, as a percent of initial, mean+/-SD) reached its nadi r for rhIGF-1 alone (58+/-5%) but was not changed by rhIGFBP-3 alone ( 99+/-4%) or rhIGF-1 plus rhIGFBP-3 (93+/-5%). In growth studies, young female hypophysectomized rats (90-105 g) were injected s.c. twice dai ly for 3-4 days, or infused s.c. for 7 days, with excipient, rhIGF-1 o r rhIGF-1 plus rhIGFBP-3 at doses similar to those used in the hypogly cemia studies. Weight gain induced by rhIGF-1 was either unchanged, or enhanced, when the rhIGF-1 was delivered with rhIGFBP-3. The hypoglyc emic activity of IGF-1 was greatly reduced if IGF-1 was administered b ound to 293-cell rhIGFBP-3 but anabolic activity was unchanged or enha nced.