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Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter

 H I Kim  ;  J W Kim  ;  S H Kim  ;  J Y Cha  ;  K S Kim  ;  Y H Ahn 
 Diabetes, Vol.49(9) : 1517-1524, 2000 
Journal Title
Issue Date
Animals ; Base Sequence ; Cell Line ; Cells, Cultured ; Chromans/pharmacology ; Consensus Sequence ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Dimerization ; Gene Expression Regulation*/drug effects ; Glucose Transporter Type 2 ; Hypoglycemic Agents/pharmacology ; Islets of Langerhans/drug effects ; Islets of Langerhans/metabolism* ; Male ; Monosaccharide Transport Proteins/genetics* ; Promoter Regions, Genetic* ; Protein Multimerization ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear/chemistry ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Receptors, Retinoic Acid/metabolism ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Proteins/metabolism ; Retinoid X Receptors ; Sequence Alignment ; Thiazoles/pharmacology ; Thiazolidinediones* ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Transcription Factors/metabolism* ; Transcription, Genetic/drug effects ; Transfection ; Tretinoin/pharmacology
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.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Kim, Ha Il(김하일)
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