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- Title
Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter.
- Authors
Kim, Ha-il; Kim, Jae-woo; Kim, Seok-Hyun; Cha, Ji-Young; Kim, Kyung-Sup; Ahn, Yong-ho; Kim, H I; Kim, J W; Kim, S H; Cha, J Y; Kim, K S; Ahn, Y H
- 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.
- Subjects
PEROXISOMES; ISLANDS of Langerhans; DRUGS; INSULIN; SECRETION
- Publication
Diabetes, 2000, Vol 49, Issue 9, p1517
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.49.9.1517