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 increti n hormone, The GLP-I receptor belongs to the family of seven transmemb rane 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 concentr ation of tissue plasminogen activator (TPA), an activator of PKC. TPA induced significantly lower GLP-I receptor mRNA levels under steady-st ate conditions after 6 and 24 h. The stability of the GLP-I receptor m RNA was unchanged. The number of GLP-I receptors present on RINm5F cel ls 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.