Butyrate, a short-chain fatty acid and histone deacetylases inhibitor: Nutritional, physiological, and pharmacological aspects in diabetes

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.