Stimulation of IGF-binding protein-1 secretion by AMP-activated protein kinase.
Insulin-like growth factor-binding protein-1 (IGFBP-1) is stimulated during intensive exercise and in catabolic conditions to very high concentrations, which are not completely explained by known regulators such as insulin and glucocorticoids. The role of AMP-activated protein kinase (AMPK), an important signaling system in lipid and carbohydrate metabolism, in regulating IGFBP-1 was studied in H4-II-E rat hepatoma cells. Arsenic(III) oxide and 5-aminoimidazole-4-carboxamide-riboside (AICAR) were used as activators. AICAR (150 microM) stimulated IGFBP-1 secretion twofold during a 5-h incubation (P = 0.002). Insulin (100 ng/ml) inhibited IGFBP-1 by 80% (P < 0.001), but this was completely abolished in the presence of 150 microM AICAR. The effect of dexamethasone in stimulating IGFBP-1 threefold was additive to the effect of AICAR (P < 0.001) and, in the presence of AICAR, was incompletely inhibited by insulin. In conclusion AMPK is identified as a novel regulatory pathway for IGFBP-1, stimulating secretion and blocking the inhibitory effect of insulin.
Lewitt
M S
MS
Department of Molecular Medicine, Karolinska Institutet, Stockholm, S-171 76, Sweden. moira@enk.ks.se
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D001152:Arsenicals; D017077:Culture Media, Conditioned; D005938:Glucocorticoids; D007328:Insulin; D007329:Insulin Antagonists; D018970:Insulin-Like Growth Factor Binding Protein 1; D009097:Multienzyme Complexes; D010087:Oxides; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D000077237:Arsenic Trioxide