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- Title
Peroxisomal Proliferator-Activated Receptor-γ Upregualtes Glucokinase Gene Expression in β-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
- Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-γ (PPAR-γ), improve peripheral insulin sensitivity and glucose-stimulated insulin secretion in pancreatic β-cells. To explore the role of PPAR-γ in glucose sensing of β-cells, we have dissected the β-cell-specific glucokinase (βGK) promoter, which constitutes glucose-sensing apparatus in pancreatic β-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The βGK-PPRE is located in the region between +47 and +68 bp. PPAR-γ/retinoid X receptor-α heterodimer binds to the element and activates the βGK promoter. The βGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-γ. PPAR-γ activates the βGK promoter in β-cells as well as non-β-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme activity in β-cell lines. These results indicate that PPAR-γ can regulate GK expression in β-cells. Taking these results together with our previous work, we conclude that PPAR-γ regulates gene expression of glucose-sensing apparatus and thereby improves glucose-sensing ability of β-cells, contributing to the restoration of β-cell function in type 2 diabetic subjects by troglitazone.
- Subjects
PEROXISOMES; PANCREATIC beta cells; GLUCOKINASE
- Publication
Diabetes, 2002, Vol 51, Issue 3, p676
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.51.3.676