Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene.

The glucagon-like peptide 1 (7-36) amide (GLP-1) receptor mediates the insulinotropic effects of the incretin hormone GLP-1. To elucidate the tissue-specific regulation of the GLP-1 receptor we screened a human genomic library with a human GLP-1 receptor cDNA. The gene spans 40 kb and consists of at least seven exons. The promoter contained no TATA- or CAAT-boxes, but several other putative cis-regulatory recognition sequences including three Sp1 binding sites. Transient transfections of GLP-1 receptor producing and non-producing cells with promoter/ reporter gene constructs revealed that the putative Sp1 binding sites and several other silencer and tissue specific elements are important for the activity. Therefore, 3000 bp upstream the GLP-1 receptor coding sequences comprise regulatory elements essential for the tissue- and cell-specific transcription of the gene.