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

78 Scopus citations

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 (US)
Pages (from-to)676-685
Number of pages10
JournalDiabetes
Volume51
Issue number3
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kim, H. I., Cha, J. Y., Kim, S. Y., Kim, J. W., Roh, K. J., Seong, J. K., Lee, N. T., Choi, K. Y., Kim, K. S., & 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