Abstract
Incidences of diabetes are increasing globally due to involvement of genetic and epigenetic factors. Phenylbutyrate (PBA) is a US FDA approved drug for treatment of urea cycle disorder in children. PBA reduces endoplasmic reticulum (ER) stress and is proven as a potent histone deacetylases (HDACs) inhibitor. Chronic ER stress results in unfolding protein response, which triggers apoptosis. Abnormal ER homoeostasis is responsible for defective processing of several genes/proteins and contributes to β-cell death/failure. Accumulated evidences indicated that HDACs modulate key biochemical pathways and HDAC inhibitors improve β-cell function and insulin resistance by modulating multiple targets. This review highlights the role of PBA on β-cell functions, insulin resistance for possible treatment of diabetes through inhibition of ER stress and HDACs.
Original language | English (US) |
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Pages (from-to) | 711-720 |
Number of pages | 10 |
Journal | Epigenomics |
Volume | 9 |
Issue number | 5 |
DOIs | |
State | Published - May 2017 |
Externally published | Yes |
Keywords
- diabetes
- ER stress
- HDAC inhibition
- phenylbutyrate
- β-cell
ASJC Scopus subject areas
- Genetics
- Cancer Research