Phenylbutyrate and β-cell function: contribution of histone deacetylases and ER stress Inhibition

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.

Keywords::

• β-cell
• diabetes
• ER stress
• HDAC inhibition
• phenylbutyrate

Acknowledgements

The authors thank VR Amara and KP Maremanda, of the Department Pharmacology and Toxicology, NIPER, SAS Nagar, Punjab, India, for English language/grammatical corrections in the present manuscript.

Financial & competing interests disclosure

This work has been funded by National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work has been funded by National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.