Regulation of glucagon-like peptide-I receptor expression and transcription by the protein kinase C pathway.
Glucagon-like peptide-I (GLP-I) is an important insulinotropic incretin hormone. The GLP-I receptor belongs to the family of seven transmembrane domain receptors. We studied the regulation of its expression by the protein kinase C (PKC)-dependent pathway in rat insulinoma RINm5F cells. Cells were incubated for 3, 6 and 24 h with an optimal concentration of tissue plasminogen activator (TPA), an activator of PKC. TPA induced significantly lower GLP-I receptor mRNA levels under steady-state conditions after 6 and 24 h. The stability of the GLP-I receptor mRNA was unchanged. The number of GLP-I receptors present on RINm5F cells was reduced after 6 and 24 h. TPA did not influence the affinity of remaining receptors to its specific ligand. These data indicate that PKC activation downregulates the expression of the GLP-I receptor gene, mainly at the transcriptional level.
Fehmann
H C
HC
Department of Medicine, Philipps University of Marburg, Germany.
Schweinfurth
J
J
Jiang
J
J
Göke
B
B
D000818:Animals; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000067757:Glucagon-Like Peptide-1 Receptor; D007340:Insulinoma / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D000242:Cyclic AMP; D011493:Protein Kinase C; D010959:Tissue Plasminogen Activator