The Role of Butyrate, A Histone Deacetylase Inhibitor in Diabetes Mellitus: Experimental Evidence for Therapeutic Intervention

Abstract

The contribution of epigenetic mechanisms in diabetes mellitus (DM), β-cell reprogramming and its complications is an emerging concept. Recent evidence suggests that there is a link between DM and histone deacetylases (HDACs), because HDAC inhibitors promote β-cell differentiation, proliferation, function and improve insulin resistance. Moreover, gut microbes and diet-derived products can alter the host epigenome. Furthermore, butyrate and butyrate-producing microbes are decreased in DM. Butyrate is a short-chain fatty acid produced from the fermentation of dietary fibers by microbiota and has been proven as an HDAC inhibitor. The present review provides a pragmatic interpretation of chromatin-dependent and independent complex signaling/mechanisms of butyrate for the treatment of Type 1 and Type 2 DM, with an emphasis on the promising strategies for its drugability and therapeutic implication.

Keywords::

• β-cell
• butyrate
• diabetes
• epigenetics
• HDAC inhibitors
• histone deacetylase
• insulin signaling

Author contributions

Both authors equally contributed to the content, review/edited and approved the final manuscript.

Acknowledgements

The authors would like to thank S Kushwaha, N Postdoctoral Fellow, Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, India as well as K Prahlad Maremanda, Senior Research Fellow of our laboratory 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, S.A.S. 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, S.A.S. 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.