Responses of insulin-like growth factor binding protein-1 (IGFBP-1) and the IGFBP-3 complex to administration of insulin-like growth factor-I.
The importance of insulin-like growth factor binding proteins (IGFBPs) in modulating the bioactivity of administered IGFs is poorly understood. This study examines responses of IGFBP-1 and the IGFBP-3 complex to recombinant human IGF-I. Eight fasted subjects received a single dose of 0.1-0.125 mg/kg IGF-I sc. This caused a 10-fold rise in IGFBP-1 over 6 h, falling rapidly after food intake. Peak (6-h) IGFBP-1 values were highly correlated with peak post-prandial (8-h) glucose values (r = 0.941). IGFBP-3 showed little response, decreasing slightly over the 48-h period following IGF-I. Adaptive changes in IGFBPs were studied in fed adults injected daily for 7 days with IGF-I, 0.1 mg/kg sc. Following the first injection, IGFBP-1 had a markedly blunted response compared to that in fasted subjects. However, after the seventh IGF-I injection, a 3.5-fold greater IGFBP-1 response to the same IGF-I dose was seen. Concomitantly with the increased IGFBP-1 responsiveness, mean immunoreactive IGFBP-3 and acid-labile subunit levels decreased significantly (p < 0.005), whereas IGFBP-2 detected by immunoblotting increased. Thus IGF-I administration causes changes in IGFBPs which may be important in regulating IGF-I bioavailability.
Baxter
R C
RC
Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Hizuka
N
N
Takano
K
K
Holman
S R
SR
Asakawa
K
K
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D004435:Eating; D005215:Fasting; D006801:Humans; D007279:Injections, Subcutaneous; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I