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

Sabbir Khan1, Sandeep K Komarya1, Gopabandhu Jena1

  • 1Facility for Risk Assessment & Intervention Studies, Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research, Sector-67, SAS Nagar, Punjab-160062, India.

Epigenomics
|May 5, 2017
PubMed

Insights

Phenylbutyrate (PBA), an FDA-approved drug, shows promise for treating diabetes by reducing endoplasmic reticulum (ER) stress and inhibiting histone deacetylases (HDACs). This approach may improve beta-cell function and insulin resistance, offering a new therapeutic avenue.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Molecular Biology

Background:

  • Global diabetes incidence is rising, driven by genetic and epigenetic factors.
  • Endoplasmic reticulum (ER) stress and histone deacetylases (HDACs) play critical roles in beta-cell dysfunction and insulin resistance.
  • Phenylbutyrate (PBA) is an FDA-approved drug known to inhibit HDACs and reduce ER stress.

Purpose of the Study:

  • To review the potential of Phenylbutyrate (PBA) as a therapeutic agent for diabetes.
  • To explore PBA's mechanisms of action, including ER stress inhibition and HDAC inhibition.
  • To evaluate PBA's impact on beta-cell function and insulin resistance.

Main Methods:

  • Review of existing scientific literature on PBA, ER stress, HDACs, and diabetes.
  • Analysis of studies investigating PBA's effects on cellular pathways related to diabetes.
  • Synthesis of evidence regarding PBA's influence on beta-cell function and insulin resistance.

Main Results:

  • Chronic ER stress contributes to beta-cell apoptosis and failure.
  • HDAC inhibition by PBA can modulate key biochemical pathways.
  • PBA demonstrates potential to improve beta-cell function and insulin sensitivity.

Conclusions:

  • PBA's ability to inhibit ER stress and HDACs suggests a promising therapeutic strategy for diabetes.
  • Further research into PBA's efficacy and safety for diabetes treatment is warranted.
  • Targeting ER stress and HDACs with PBA may offer a novel approach to managing diabetes.

Keywords:
ER stressHDAC inhibitiondiabetesphenylbutyrateβ-cell

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