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Peroxisomal proliferator-activated receptor-gamma upregulates glucokinase gene expression in beta-cells

Authors
 Ha-il Kim  ;  Ji-Young Cha  ;  So-Youn Kim  ;  Jae-woo Kim  ;  Kyung Jin Roh  ;  Je-Kyung Seong  ;  Nam Taek Lee  ;  Kang-Yell Choi  ;  Kyung-Sup Kim  ;  Yong-ho Ahn 
Citation
 Diabetes, Vol.51(3) : 676-685, 2002 
Journal Title
 Diabetes 
ISSN
 0012-1797 
Issue Date
2002
Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-gamma (PPAR-gamma), improve peripheral insulin sensitivity and glucose-stimulated insulin secretion in pancreatic beta-cells. To explore the role of PPAR-gamma in glucose sensing of beta-cells, we have dissected the beta-cell-specific glucokinase (betaGK) promoter, which constitutes glucose-sensing apparatus in pancreatic beta-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The betaGK-PPRE is located in the region between +47 and +68 bp. PPAR-gamma/retinoid X receptor-alpha heterodimer binds to the element and activates the betaGK promoter. The betaGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-gamma. PPAR-gamma activates the betaGK promoter in beta-cells as well as non-beta-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme activity in beta-cell lines. These results indicate that PPAR-gamma can regulate GK expression in beta-cells. Taking these results together with our previous work, we conclude that PPAR-gamma regulates gene expression of glucose-sensing apparatus and thereby improves glucose-sensing ability of beta-cells, contributing to the restoration of beta-cell function in type 2 diabetic subjects by troglitazone.
Full Text
http://diabetes.diabetesjournals.org/content/51/3/676.long
DOI
10.2337/diabetes.51.3.676
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
김재우(Kim, Jae Woo) ORCID logo https://orcid.org/0000-0001-5456-9495
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143318
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