| Item type |
文献 / Documents(1) |
| 公開日 |
2020-07-29 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0115350 |
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言語 |
ja |
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関連名称 |
10.1371/journal.pone.0115350 |
| 出版タイプ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Long-Term Pancreatic Beta Cell Exposure to High Levels of Glucose but Not Palmitate Induces DNA Methylation within the Insulin Gene Promoter and Represses Transcriptional Activity |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Glucotoxicity Induces Insulin Promoter DNA Methylation in Beta Cells |
|
言語 |
en |
| 著者 |
イシカワ, コウタ
ツネカワ, シン
イケニワ, マコト
イズモト, タカコ
イイダ, アツシ
オガタ, ヒデタダ
ウエニシ, エイタ
セイノ, ユウスケ
オザキ, ノブアキ
スギムラ, ヨシヒサ
ハマダ, ヨウジ
黒田, 暁生
シンジョウ, ケイコ
コンドウ, ユタカ
オオイソ, ユタカ
|
| 抄録 |
|
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内容記述タイプ |
Abstract |
|
内容記述 |
Recent studies have implicated epigenetics in the pathophysiology of diabetes. Furthermore, DNA methylation, which irreversibly deactivates gene transcription, of the insulin promoter, particularly the cAMP response element, is increased in diabetes patients. However, the underlying mechanism remains unclear. We aimed to investigate insulin promoter DNA methylation in an over-nutrition state. INS-1 cells, the rat pancreatic beta cell line, were cultured under normal-culture-glucose (11.2 mmol/l) or experimental-high-glucose (22.4 mmol/l) conditions for 14 days, with or without 0.4 mmol/l palmitate. DNA methylation of the rat insulin 1 gene (Ins1) promoter was investigated using bisulfite sequencing and pyrosequencing analysis. Experimental-high-glucose conditions significantly suppressed insulin mRNA and increased DNA methylation at all five CpG sites within the Ins1 promoter, including the cAMP response element, in a time-dependent and glucose concentration-dependent manner. DNA methylation under experimental-high-glucose conditions was unique to the Ins1 promoter; however, palmitate did not affect DNA methylation. Artificial methylation of Ins1 promoter significantly suppressed promoter-driven luciferase activity, and a DNA methylation inhibitor significantly improved insulin mRNA suppression by experimental-high-glucose conditions. Experimental-high-glucose conditions significantly increased DNA methyltransferase activity and decreased ten-eleven-translocation methylcytosine dioxygenase activity. Oxidative stress and endoplasmic reticulum stress did not affect DNA methylation of the Ins1 promoter. High glucose but not palmitate increased ectopic triacylglycerol accumulation parallel to DNA methylation. Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation. Finally, DNA methylation of the Ins1 promoter increased in isolated islets from Zucker diabetic fatty rats. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells. It provides new insights into the irreversible pathophysiology of diabetes. |
|
言語 |
en |
| 書誌情報 |
en : PLOS ONE
巻 10,
号 2,
p. e0115350,
発行日 2015-02-06
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19326203 |
| 出版者 |
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出版者 |
PLOS |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2015 Ishikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
291422 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
pone_10_2_e0115350.pdf (1.65 MB)
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