A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS)
A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS)
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DOI：
10.1016/j.abb.2008.04.015
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发表时间：
2008-07-15
影响因子：
3.9
通讯作者：
Kang, Yup
中科院分区：
文献类型：
--
作者：
Choi, Sung-E;Lee, Youn-Jung;Kang, Yup
游离脂肪酸（FFA）被认为是引起 β 细胞功能障碍的刺激物。本研究旨在确定内质网 (ER) 应激是否参与棕榈酸酯诱导的葡萄糖刺激胰岛素分泌 (GSIS) 抑制，以及使用化学伴侣减少 ER 应激是否可以恢复 GSIS 抑制。用 300 μM 棕榈酸酯处理 INS-1 细胞 24 小时引发 ER 应激，显示磷酸化 eF2 α、Bip 和剪接 XBP 水平增加，并且还诱导 GSIS 抑制而不降低细胞活力。补充 4-苯基丁酸 (4-PBA) 作为化学伴侣可减少棕榈酸酯诱导的 ER 应激，并显着逆转棕榈酸酯诱导的 GSIS 抑制。此外，4-PBA 改善了原代大鼠胰岛细胞中棕榈酸盐诱导的 GSIS 抑制。这些数据表明，ER 应激参与了 FFA 诱导的 GSIS 抑制，并且 FFA 诱导的 β 细胞功能障碍可以通过化学伴侣治疗得到改善。 (C) 2008 Elsevier Inc. 保留所有权利。
Free fatty acids (FFAs) are believed to be a stimulus to elicit beta cell dysfunction. The present study was undertaken to determine whether endoplasmic reticulum (ER) stress was involved in palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS) and whether reduction of ER stress using a chemical chaperone restored the GSIS-inhibition. Treatment of INS-1 cells with 300 mu M palmitate for 24 h elicited ER stress, showing increased levels of phospho-elF2 alpha, Bip and spliced XBP, and also induced GSIS-inhibition without reduction of cell viability. Replenishment with 4-phenyl butyric acid (4-PBA) as a chemical chaperone reduced the palmitate-induced-ER stress and significantly reversed the palmitate-induced GSIS-inhibition. Furthermore, 4-PBA ameliorated palmitate-induced GSIS-inhibition in primary rat islet cells. These data suggested that ER stress was involved in FFA-induced GSIS-inhibition and that the FFA-induced beta cell dysfunction could be ameliorated by treatment with a chemical chaperone. (C) 2008 Elsevier Inc. All rights reserved.