title: 4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated pancreatic β-cell apoptosis in rats with streptozotocin-induced diabetes.
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.
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, 72 Guangzhou Rd, Nanjing, 210008, Jiangsu, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Mei
authors.initials: M
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Fei
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Pan
authors.forename: Qian-Qi
authors.initials: QQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D010654:Phenylbutyrates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D010654:Phenylbutyrates; D013311:Streptozocin; C075773:4-phenylbutyric acid