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

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Handbook of Nutrition, Diet, and Epigenetics

Abstract

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.

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Abbreviations

AMPK:

AMP-activated protein kinase

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-regulated kinase

FFAR:

Free fatty acid receptor

Foxp3:

Forkhead box P3

GLP-1:

Glucagon-like peptide-1

GLUT:

Glucose transporter

GPCR:

G-protein-coupled receptor

HATs:

Histone acetyltransferases

HDACs:

Histone deacetylases

HFD:

High-fat diet

iNOS:

Inducible nitric oxide synthase

IRS:

Insulin receptor substrate

MAPK:

Mitogen-activated protein kinase

NF-κB:

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

Pdx1:

Pancreatic duodenal homeobox 1

PI3K:

Phosphatidylinositide 3-kinase

PPARγ:

Peroxisome proliferator-activated receptor-γ

SCFA:

Short-chain fatty acid

T1D/T2D:

Type 1 and type 2 diabetes mellitus

TGF-β1:

Transforming growth factor beta1

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Authors and Affiliations

  1. Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    Sabbir Khan, Krishna Prahlad Maremanda & Gopabandhu Jena

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  1. Sabbir Khan
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  2. Krishna Prahlad Maremanda
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  3. Gopabandhu Jena
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Correspondence to Gopabandhu Jena .

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  1. c/o Editorial Board 978-0-387-78665 , Heidelberg, Baden-Württemberg, Germany

    Vinood Patel

  2. Kings College , London, United Kingdom

    Victor Preedy

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Khan, S., Maremanda, K.P., Jena, G. (2017). Butyrate, a Short-Chain Fatty Acid and Histone Deacetylases Inhibitor: Nutritional, Physiological, and Pharmacological Aspects in Diabetes. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-31143-2_70-1

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  • DOI: https://doi.org/10.1007/978-3-319-31143-2_70-1

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