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4-Phenylbutyric acid attenuates endoplasmic reticulum stress-mediated pancreatic β-cell apoptosis in rats with streptozotocin-induced diabetes

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Abstract

Endoplasmic reticulum stress (ERS) plays an important role in diabetes mellitus (DM), but the association between DM and ERS is unknown. We have previously shown that streptozotocin (STZ)-induced diabetes in rats is characterized by increased levels of ERS markers. Here, we tested whether the chemical chaperone 4-phenylbutyric acid (4-PBA) ameliorated ERS-associated apoptosis in pancreatic β-cells in rats with STZ-induced diabetes. Male Sprague–Dawley rats were divided into 3 groups: control group, DM group, and DM model plus 4-PBA treatment group (4-PBA group). DM model rats were induced by injection of STZ (60 mg/kg) intraperitoneally, and 4-PBA was administered daily by gavage at a dose of 500 mg/kg body weight for 20 days. β-cell apoptosis was higher in the DM group than in the control group. Moreover, the expression of caspase-3, Bax, and the ERS indicators Bip and CHOP was markedly elevated in the pancreas of rats in the DM group, whereas the expression of Bcl-2 was lower in these rats (P < 0.05). Blood glucose concentration in diabetic rats gradually decreased with 4-PBA treatment but remained higher at the end of the experiment compared to the concentration in control rats. Consistent with this, 4-PBA raised the fasting insulin level in diabetic rats; it also suppressed the expression of caspase-3, Bax, and ERS indicators but enhanced the expression of Bcl-2. In conclusion, 4-PBA protects pancreatic β-cells from apoptosis in STZ-induced diabetes by attenuating the severity of ERS.

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Abbreviations

ERS:

Endoplasmic reticulum stress

H&E:

Hematoxylin & eosin

4-PBA:

4-phenylbutyric acid

RT-PCR:

Reverse transcription-polymerase chain reaction

STZ:

Streptozotocin

T1DM:

Type 1 diabetes mellitus

TUNEL:

Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling

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Acknowledgments

This work was supported by the Science Foundation of Jiangsu Educational Committee of China (No. 07KJD320144).

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All authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Endocrinology, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, 72 Guangzhou Rd, Nanjing, 210008, Jiangsu, People’s Republic of China

    Min Zhu & Qian-qi Liu

  2. Institute of Pediatrics, Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China

    Mei Guo, Li Fei & Xiao-qin Pan

Authors
  1. Min Zhu
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  2. Mei Guo
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  3. Li Fei
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  4. Xiao-qin Pan
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  5. Qian-qi Liu
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Correspondence to Qian-qi Liu.

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Zhu, M., Guo, M., Fei, L. et al. 4-Phenylbutyric acid attenuates endoplasmic reticulum stress-mediated pancreatic β-cell apoptosis in rats with streptozotocin-induced diabetes. Endocrine 47, 129–137 (2014). https://doi.org/10.1007/s12020-013-0132-7

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