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 unknown. We have tested the ability of rhIGFBP-3, made in 293 cells or CHO cells, to affect the glycemic and anabolic activities of co-administered rhIGF-1. For glycemic studies female dw/dw rats were anesthetized, a jugular catheter inserted, basal blood samples taken and i.v. injections 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 glucose (20 min later, as a percent of initial, mean +/- SD) reached its nadir 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 daily for 3-4 days, or infused s.c. for 7 days, with excipient, rhIGF-1 or rhIGF-1 plus rhIGFBP-3 at doses similar to those used in the hypoglycemia studies. Weight gain induced by rhIGF-1 was either unchanged, or enhanced, when the rhIGF-1 was delivered with rhIGFBP-3. The hypoglycemic activity of IGF-1 was greatly reduced if IGF-1 was administered bound to 293-cell rhIGFBP-3 but anabolic activity was unchanged or enhanced.
Clark
R G
RG
Genentech, Inc., South San Francisco, CA 94080.
Mortensen
D
D
Reifsynder
D
D
Mohler
M
M
Etcheverry
T
T
Mukku
V
V
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006128:Growth / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007016:Hypophysectomy; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D006131:Growth Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I