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TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS
Free fatty acids (FFAs) are cytotoxic to pancreatic islet β-cells and play a crucial role in the diabetes disease process. A recent study revealed a down-regulation of transcription factor 2 (TCF2) levels during FFA-mediated cytotoxicity in pancreatic β-cells. However, its function during this proce...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159796/ https://www.ncbi.nlm.nih.gov/pubmed/25079440 http://dx.doi.org/10.3390/ijms150813317 |
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author | Quan, Xiaojuan Zhang, Lin Li, Yingna Liang, Chunlian |
author_facet | Quan, Xiaojuan Zhang, Lin Li, Yingna Liang, Chunlian |
author_sort | Quan, Xiaojuan |
collection | PubMed |
description | Free fatty acids (FFAs) are cytotoxic to pancreatic islet β-cells and play a crucial role in the diabetes disease process. A recent study revealed a down-regulation of transcription factor 2 (TCF2) levels during FFA-mediated cytotoxicity in pancreatic β-cells. However, its function during this process and the underlying mechanism remains unclear. In this study, treatment with palmitic acid (PA) at high levels (400 and 800 μM) decreased β-cell viability and TCF2 protein expression, along with the glucose-stimulated insulin secretion (GSIS). Western and RT-PCR analysis confirmed the positive regulatory effect of TCF2 on GSIS through promotion of the key regulators pancreatic duodenal homeobox-1 (PDX1) and glucose transporter 2 (GLUT2) in β-cells. In addition, both PI3K/AKT and MEK/ERK showed decreased expression in PA (800 μM)-treated β-cells. Overexpression of TCF2 could effectively restore the inhibitory effect of PA on the activation of PI3K/AKT and MEK/ERK as well as β-cell viability, simultaneously, inhibited PA-induced reactive oxygen species (ROS) generation. After blocking the PI3K/AKT and MAPK/ERK signals with their specific inhibitor, the effect of overexpressed TCF2 on β-cell viability and ROS production was obviously attenuated. Furthermore, a protective effect of TCF2 on GSIS by positive modulation of JNK-PDX1/GLUT2 signaling was also confirmed. Accordingly, our study has confirmed that TCF2 positively modulates insulin secretion and further inhibits ROS generation via the PI3K/AKT and MEK/ERK signaling pathways. Our work may provide a new therapeutic target to achieve prevention and treatment of diabetes. |
format | Online Article Text |
id | pubmed-4159796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-41597962014-09-18 TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS Quan, Xiaojuan Zhang, Lin Li, Yingna Liang, Chunlian Int J Mol Sci Article Free fatty acids (FFAs) are cytotoxic to pancreatic islet β-cells and play a crucial role in the diabetes disease process. A recent study revealed a down-regulation of transcription factor 2 (TCF2) levels during FFA-mediated cytotoxicity in pancreatic β-cells. However, its function during this process and the underlying mechanism remains unclear. In this study, treatment with palmitic acid (PA) at high levels (400 and 800 μM) decreased β-cell viability and TCF2 protein expression, along with the glucose-stimulated insulin secretion (GSIS). Western and RT-PCR analysis confirmed the positive regulatory effect of TCF2 on GSIS through promotion of the key regulators pancreatic duodenal homeobox-1 (PDX1) and glucose transporter 2 (GLUT2) in β-cells. In addition, both PI3K/AKT and MEK/ERK showed decreased expression in PA (800 μM)-treated β-cells. Overexpression of TCF2 could effectively restore the inhibitory effect of PA on the activation of PI3K/AKT and MEK/ERK as well as β-cell viability, simultaneously, inhibited PA-induced reactive oxygen species (ROS) generation. After blocking the PI3K/AKT and MAPK/ERK signals with their specific inhibitor, the effect of overexpressed TCF2 on β-cell viability and ROS production was obviously attenuated. Furthermore, a protective effect of TCF2 on GSIS by positive modulation of JNK-PDX1/GLUT2 signaling was also confirmed. Accordingly, our study has confirmed that TCF2 positively modulates insulin secretion and further inhibits ROS generation via the PI3K/AKT and MEK/ERK signaling pathways. Our work may provide a new therapeutic target to achieve prevention and treatment of diabetes. MDPI 2014-07-30 /pmc/articles/PMC4159796/ /pubmed/25079440 http://dx.doi.org/10.3390/ijms150813317 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Quan, Xiaojuan Zhang, Lin Li, Yingna Liang, Chunlian TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title | TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title_full | TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title_fullStr | TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title_full_unstemmed | TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title_short | TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS |
title_sort | tcf2 attenuates ffa-induced damage in islet β-cells by regulating production of insulin and ros |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159796/ https://www.ncbi.nlm.nih.gov/pubmed/25079440 http://dx.doi.org/10.3390/ijms150813317 |
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