Butyrate, a Short-Chain Fatty Acid and Histone Deacetylases Inhibitor: Nutritional, Physiological, and Pharmacological Aspects in Diabetes

  • Sabbir Khan
  • Krishna Prahlad Maremanda
  • Gopabandhu JenaEmail author
Reference work entry


Diabetes is a complex metabolic disease and its incidences are growing at an alarming rate globally. Recent evidences suggest that there is a link between diabetes and histone deacetylases (HDACs), because HDAC inhibitors promote beta cell proliferation and function as well as reduce insulin-resistance and gluconeogenesis. Gut microbes play an important role in pathogenesis of various diseases including diabetes and can modulate the host epigenome. Notably, butyrate level and butyrate-producing microbes are decreased in diabetic animal as well as patients. Butyrate is a short-chain fatty acid naturally produced in large intestine (colon) from the fermentation of dietary fibers by microbes and is also found in butter and cheese. Butyrate has been established as a HDAC inhibitor in several in vitro and in vivo experiments and affects the expression of various genes, which are directly and indirectly involved in glucose metabolism and pathogenesis of diabetes. This chapter discusses the contribution of HDACs and their inhibition by butyrate in possible pharmacotherapy of diabetes. The present chapter also highlights molecular mechanisms of butyrate for treatment of type 1 and type 2 diabetes as well as the challenges and strategies for its therapeutic implication as a promising antidiabetic molecule.


Beta cell Butyrate Diabetes Epigenetics Fiber Histone deacetylaces HDAC inhibitors Insulin Insulin-resistance Histone acetylation Short-chain fatty acid Metabolic disorders 

List of Abbreviations


AMP-activated protein kinase


Endothelial nitric oxide synthase


Extracellular signal-regulated kinase


Free fatty acid receptor


Forkhead box P3


Glucagon-like peptide-1


Glucose transporter


G-protein-coupled receptor


Histone acetyltransferases


Histone deacetylases


High-fat diet


Inducible nitric oxide synthase


Insulin receptor substrate


Mitogen-activated protein kinase


Nuclear factor kappa-light-chain-enhancer of activated B cells


Pancreatic duodenal homeobox 1


Phosphatidylinositide 3-kinase


Peroxisome proliferator-activated receptor-γ


Short-chain fatty acid


Type 1 and type 2 diabetes mellitus


Transforming growth factor beta1


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sabbir Khan
    • 1
  • Krishna Prahlad Maremanda
    • 1
  • Gopabandhu Jena
    • 1
    Email author
  1. 1.Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research (NIPER)MohaliIndia

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