title: Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter.
abstract: We identified the peroxisomal proliferator response element (PPRE) in the +68/+89 region of the rat GLUT2 gene. To identify whether the putative PPRE in the GLUT2 gene (GLUT2-PPRE) is functional, GLUT2 promoter-luciferase reporter constructs were transfected into CV-1 cells. Promoter activities were increased by coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma, retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and 9-cis retinoic acid potentiated the transactivational effects. Introduction of mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR-gamma/RXR-alpha heterodimer. Electrophoretic mobility shift assay using nuclear extracts of CV-1 cells, which were transfected with various combinations of PPARs or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and RXR-alpha preferentially bound to GLUT2-PPRE. In HIT-T15 cells, promoter activity of the rat GLUT2 gene was increased by troglitazone and 9-cis retinoic acid, and mutations of GLUT2-PPRE resulted in reduction of promoter activity. In addition, we observed increased GLUT2 transcription by troglitazone and 9-cis retinoic acid in isolated rat primary islets. These results suggested that the GLUT2-PPRE is functional and plays a significant role in gene expression of GLUT2 in pancreatic beta-cells. This is the first report identifying PPRE in a gene involved in glucose homeostasis, linking the effect of troglitazone on the regulation of insulin secretion.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Genetic Sciences, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H I
authors.initials: HI
authors.lastname: Kim
authors.forename: J W
authors.initials: JW
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: J Y
authors.initials: JY
authors.lastname: Cha
authors.forename: K S
authors.initials: KS
authors.lastname: Kim
authors.forename: Y H
authors.initials: YH
authors.lastname: Ahn
mesh_terms: D000077556:Alitretinoin; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D016415:Sequence Alignment; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; D004268:DNA-Binding Proteins; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; D000077288:Troglitazone