Peroxisomal proliferator-activated receptor-γ upregulates glucokinase gene expression in β-cells

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

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 PRAR-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.

Original languageEnglish
Pages (from-to)676-685
Number of pages10
JournalDiabetes
Volume51
Issue number3
DOIs
Publication statusPublished - 2002 Jan 1

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Glucokinase
Up-Regulation
Gene Expression
troglitazone
Response Elements
Glucose
Retinoid X Receptors
glucokinase receptor
Thiazolidinediones
Insulin Resistance
Insulin
Ligands
Cell Line
Mutation
Enzymes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kim, H. I., Cha, J. Y., Kim, S. Y., Kim, J. W., Roh, K. J., Seong, J. K., ... Ahn, Y. H. (2002). Peroxisomal proliferator-activated receptor-γ upregulates glucokinase gene expression in β-cells. Diabetes, 51(3), 676-685. https://doi.org/10.2337/diabetes.51.3.676
Kim, Ha Il ; Cha, Ji Young ; Kim, So Youn ; Kim, Jae Woo ; Roh, Kyung Jin ; Seong, Je Kyung ; Lee, Nam Taek ; Choi, Kang-Yell ; Kim, Kyung Sup ; Ahn, Yong Ho. / Peroxisomal proliferator-activated receptor-γ upregulates glucokinase gene expression in β-cells. In: Diabetes. 2002 ; Vol. 51, No. 3. pp. 676-685.
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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 PRAR-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.",
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Kim, HI, Cha, JY, Kim, SY, Kim, JW, Roh, KJ, Seong, JK, Lee, NT, Choi, K-Y, Kim, KS & Ahn, YH 2002, 'Peroxisomal proliferator-activated receptor-γ upregulates glucokinase gene expression in β-cells', Diabetes, vol. 51, no. 3, pp. 676-685. https://doi.org/10.2337/diabetes.51.3.676

Peroxisomal proliferator-activated receptor-γ upregulates glucokinase gene expression in β-cells. / Kim, Ha Il; Cha, Ji Young; Kim, So Youn; Kim, Jae Woo; Roh, Kyung Jin; Seong, Je Kyung; Lee, Nam Taek; Choi, Kang-Yell; Kim, Kyung Sup; Ahn, Yong Ho.

In: Diabetes, Vol. 51, No. 3, 01.01.2002, p. 676-685.

Research output: Contribution to journalArticle

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AU - Kim, Ha Il

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AU - Seong, Je Kyung

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AU - Choi, Kang-Yell

AU - Kim, Kyung Sup

AU - Ahn, Yong Ho

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N2 - 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 PRAR-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.

AB - 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 PRAR-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.

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