Insulin-like growth factor binding protein-1 from Hep G2 cells is potently inhibited by the truncated IGF-I analogue des-(1-3) IGF-I.
Des-(1-3) insulin-like growth factor-I (IGF-I) is an IGF analogue lacking aminoacid 1 to 3 which displays reduced binding to insulin-like growth factor binding protein-1 (IGFBP-1). A greater inhibition of immunoreactive IGFBP-1 was obtained with des-(1-3) IGF-I (10 ng/ml) in Hep G2 medium when incubated in Eagle's Modified Essential Medium (EMEM) without phenolred compared to EMEM with phenolred; EMEM without phenolred was chosen for further experiments. Des-(1-3)IGF-I decreases dose dependently the concentration of IGFBP-1, with a maximal effect at 3-10 micrograms/l when incubated for 24 h; 10 micrograms/l of des-(1-3)IGF-I caused a small but significant inhibition of IGFBP-1 after 8 h incubation and this inhibition was 41% and 33% of controls after 14 and 19 h incubation. The relative potencies at 16 h of incubation of IGF-I and insulin in suppressing IGFBP-1 in comparison to des-(1-3)IGF-I were 0.41 (0.25-0.78) and 0.08 (0.01-0.26), respectively. A dose-dependent decrease of IGFBP-1 mRNA to 30% of control was observed after 4 h incubation with 0.1-10 micrograms/l des-(1-3)IGF-I. Changes of glucose concentration (0-20 mmol/l) in the medium did not affect the IGFBP-1 concentration in the medium. In summary: Des-(1-3)IGF-I was tenfold more potent than insulin, and threefold more potent than IGF-I in decreasing IGFBP-1 concentration in medium conditioned by Hep G2 cells.
Lindgren
B F
BF
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Isaksson
M
M
Stern
I
I
Hall
K
K
D000704:Analysis of Variance; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003470:Culture Media; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010637:Phenolsulfonphthalein; D012313:RNA / Q000032:analysis; D011863:Radioimmunoassay; D013002:Somatomedins / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D003470:Culture Media; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D010446:Peptide Fragments; D013002:Somatomedins; C058957:insulin-like growth factor 1, des-(1-3)-; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D010637:Phenolsulfonphthalein; D005947:Glucose