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Int. J. Mol. Sci. 2014, 15(8), 13317-13332;

TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS

Department of Geriatrics, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China
Authors to whom correspondence should be addressed.
Received: 20 April 2014 / Revised: 5 June 2014 / Accepted: 18 June 2014 / Published: 30 July 2014
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: β-cells; free fatty acids; TCF2; insulin; reactive oxygen species β-cells; free fatty acids; TCF2; insulin; reactive oxygen species

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Quan, X.; Zhang, L.; Li, Y.; Liang, C. TCF2 Attenuates FFA-Induced Damage in Islet β-Cells by Regulating Production of Insulin and ROS. Int. J. Mol. Sci. 2014, 15, 13317-13332.

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