4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phen...

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Main Authors: Yu-pu Hong, Wen-yi Guo, Wei-xing Wang, Liang Zhao, Ming-wei Xiang, Fang-chao Mei, Ablikim Abliz, Peng Hu, Wen-hong Deng, Jia Yu
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2016/4592346
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author Yu-pu Hong
Wen-yi Guo
Wei-xing Wang
Liang Zhao
Ming-wei Xiang
Fang-chao Mei
Ablikim Abliz
Peng Hu
Wen-hong Deng
Jia Yu
author_facet Yu-pu Hong
Wen-yi Guo
Wei-xing Wang
Liang Zhao
Ming-wei Xiang
Fang-chao Mei
Ablikim Abliz
Peng Hu
Wen-hong Deng
Jia Yu
author_sort Yu-pu Hong
collection DOAJ
description Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.
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publishDate 2016-01-01
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series International Journal of Endocrinology
spelling doaj-art-8fe24e75954c40b38382e99b0d2ac2bb2025-02-03T01:31:41ZengWileyInternational Journal of Endocrinology1687-83371687-83452016-01-01201610.1155/2016/459234645923464-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute PancreatitisYu-pu Hong0Wen-yi Guo1Wei-xing Wang2Liang Zhao3Ming-wei Xiang4Fang-chao Mei5Ablikim Abliz6Peng Hu7Wen-hong Deng8Jia Yu9Department of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei Province 430060, ChinaEndoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.http://dx.doi.org/10.1155/2016/4592346
spellingShingle Yu-pu Hong
Wen-yi Guo
Wei-xing Wang
Liang Zhao
Ming-wei Xiang
Fang-chao Mei
Ablikim Abliz
Peng Hu
Wen-hong Deng
Jia Yu
4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
International Journal of Endocrinology
title 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
title_full 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
title_fullStr 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
title_full_unstemmed 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
title_short 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis
title_sort 4 phenylbutyric acid attenuates pancreatic beta cell injury in rats with experimental severe acute pancreatitis
url http://dx.doi.org/10.1155/2016/4592346
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