Inhibitors of glucose uptake stimulate the production of insulin-like growth factor-binding protein (IGFBP-1) by human fetal liver.
Cultured human fetal hepatic explants were used to study the role of hexose uptake in regulating production of the GH-independent insulin-like growth factor-binding protein (IGFBP-1). Cytochalasin B (100 microM), but not cytochalasin E, inhibited 2-deoxyglucose uptake by fetal liver explants and increased production of IGFBP-1 2-fold. Two agents which stimulate cyclic nucleotide-dependent pathways, cholera toxin and theophylline, also inhibited 2-deoxyglucose uptake in this system and both stimulated IGFBP-1 production. When added to a maximally inhibiting concentration of cytochalasin B (250 microM), hexose uptake was not further inhibited by theophylline (5 mM) or cholera toxin (10 micrograms/ml), suggesting that the three substances interact with the same hexose transport mechanism. However, the stimulatory effect of theophylline (5 mM) or cholera toxin (10 micrograms/ml) on IGFBP-1 production was additive to the effect of 250 microM cytochalasin B, suggesting that another pathway, possibly involving cyclic nucleotide accumulation, could further stimulate IGFBP-1 above the effect of blocking glucose transport. Insulin (300 nM) had no effect on hexose uptake by human fetal liver explants but inhibited IGFBP-1 production, both basally and when stimulated by cytochalasin B (100 microM) or cholera toxin (1 microgram/ml). These results are consistent with the conclusion that a cyclic nucleotide-dependent pathway, activated by blocking hexose transport and inhibited by insulin, is involved in the regulation of IGFBP-1 synthesis.
Lewitt
M S
MS
Department of Medicine, University of Sydney, New South Wales, Australia.
Baxter
R C
RC
D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis*; D002772:Cholera Toxin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000037:antagonists & inhibitors*; D006601:Hexoses / Q000037:antagonists & inhibitors; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D002352:Carrier Proteins; D006601:Hexoses; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D003571:Cytochalasin B; D002772:Cholera Toxin; D003847:Deoxyglucose; D013806:Theophylline; D005947:Glucose