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Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro

SU Jie-ying LI Hong-liang YANG Wen-ying XIAO Jian-zhong DU Rui-qin SHEN Xiao-xia CAI Zhe ZHANG Lan SHU Jun

中华医学杂志（英文版）2010，Vol.123Issue(17)：2416-2423,8.

中华医学杂志（英文版）2010，Vol.123Issue(17)：2416-2423,8.DOI:10.3760/cma.j.issn.0366-6999.2010.17.024

Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro

SU Jie-ying ¹LI Hong-liang ²YANG Wen-ying ³XIAO Jian-zhong ²DU Rui-qin ²SHEN Xiao-xia ⁴CAI Zhe ²ZHANG Lan ⁵SHU Jun⁵

作者信息

1. Graduate School, Peking Union Medical College, Tsinghua University, Beijing 100730, China
2. Department of Endocrinology, China-Japan Friendship Hospital,Beijing 100029, China
3. Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City,OK, 73104, USA
4. Department of Endocrinology, General Hospital of the Second Artilleryman of Chinese People's Liberation Army, Beijing 100088, China
5. Department of Immunology and Tissue Engineering, Clinical Research Institute of China-Japan Friendship Hospital, Beijing 100029, China
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摘要

Abstract

Background Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However,whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells.Methods The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed.Results Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion.Conclusion UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway.

关键词

pancreatic alpha cells/uncoupling protein 2/glucagon/free fatty acids

Key words

pancreatic alpha cells/uncoupling protein 2/glucagon/free fatty acids

引用本文复制引用

SU Jie-ying,LI Hong-liang,YANG Wen-ying,XIAO Jian-zhong,DU Rui-qin,SHEN Xiao-xia,CAI Zhe,ZHANG Lan,SHU Jun..Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro [J].中华医学杂志（英文版）,2010,123(17):2416-2423,8.

基金项目

This study was supported by a grant from the Clinical Research Institute of China-Japan Friendship Hospital. （）

中华医学杂志（英文版）

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ISSN：0366-6999

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