Glucagon-like peptide 1 increases glucose-dependent activity of the homeoprotein IDX-1 transactivating domain in pancreatic beta-cells.
Both glucose and glucagon-like peptide 1 (GLP-1) stimulate insulin gene transcription in endocrine pancreatic beta-cells within the islets of Langerhans. The effects of glucose are mediated by the homeodomain transcription factor islet duodenum homeobox -1 (IDX-1) that binds to two adenine thymidine-rich (A1 and A2/3) motifs within the rat insulin promoter. Glucose stimulates the activity of the transactivation domain of IDX-1 that lies within the first 80 amino acids of the IDX-1 protein. The effects of GLP-1 on insulin gene expression are primarily conferred by the cAMP responsive element (CRE) within the insulin promoter. GLP-1 stimulates glucose-dependent insulin release from beta-cells. We hypothesize that GLP-1 may augment the effects of glucose on insulin gene transcription. Here we show that GLP-1 stimulates insulin gene transcription independent of the CRE and is glucose-dependent. Furthermore, we show that GLP-1 stimulates the transactivational activity of IDX-1.
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, Massachusetts, USA.
M A
MA
Hussain
J F
JF
Habener
D000818:Animals; D002460:Cell Line; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D007515:Islets of Langerhans / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D018398:Homeodomain Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose