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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

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.

Keywords

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

List of 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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Copyright information

© 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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