Abstract: Objective To evaluate the effect of 4-PBA in high-fat diets-fed with/without streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Methods Type 2 diabetic animal model was developed by high-fat diets-fed with/without low-dose STZ injection. Diabetic rats were orally gavages each day with 4-PBA for 20 days. The expressions of mRNA and protein were detected by real-time PCR and Western blot analysis. Results 4-PBA treatment significantly reduced the pancreas apoptosis induced by high-fat diets-fed with/without STZ. High-fat diets with/without STZ-induced increase in expression of CHOP mRNA and protein, p53 mRNA, Bax mRNA and protein, and cytochrome c protein, decrease in mRNA and protein levels of Bcl-2 were attenuated by 4-PBA treatment. 4-PBA also attenuated the increase of ERK1/2 phosphorylation induced by high-fat diets with/without STZ. Conclusion Treatment with 4-PBA significantly inhibits the process of type 2 diabetes in rats through the ER stress and mitochondria-dependent apoptotic pathway.

Key words: type 2 diabetic rat, endoplasmic reticulum stress, apoptosis, 4-phenylbutyric acid, CHOP