Glucagon and GLP-1 stimulate IGFBP-1 secretion in Hep G2 cells without effect on IGFBP-1 mRNA.
Glucagon has previously been reported to increase serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) in humans. The in vitro effect of glucagon and glucagon-like peptide-1 (7-36) amide (GLP-1) was investigated in Hep G2 human hepatoma cells. The expression of IGFBP-1 mRNA was determined by solution hybridization assay and IGFBP-1 secretion was measured by radioimmunoassay. In contrast to forskolin the peptides glucagon and GLP-1 had no effect on IGFBP-1 mRNA at 3, 6 and 24 h incubation or any detectable effect on the apparent half-life of IGFBP-1 mRNA. However, the exposure to glucagon (10 microg/mL, 2.87 microM) and GLP-1 (1 microM) caused a two-fold stimulation in protein levels of IGFBP-1 after 6 h incubation, declining to control levels after 24 h. This transient effect was dose dependent, remained when transcription was inhibited and required protein synthesis. The regulation of IGFBP-1 secretion by glucagon and GLP-1 appeared to be cAMP independent. In conclusion, glucagon and GPL-1 were shown to have a post-transcriptional stimulatory effect on IGFBP-1 release.
Department of Molecular Medicine, The Endocrine and Diabetes Unit, Karolinska Institute, S-171 76, Stockholm, Sweden.
Agneta
A
Hilding
Christer
C
Möller
Kerstin E
KE
Hall
D029742:Caenorhabditis elegans Proteins; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051880:Receptors, Notch; D013997:Time Factors; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D018970:Insulin-Like Growth Factor Binding Protein 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D005934:Glucagon; D000242:Cyclic AMP