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.

Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

“…Tolhurst et al demonstrated that short fatty acids stimulate the secretion of GLP-1 in vitro [34]. Also, some suggest that there is a relationship between the short fatty acid as histone deacetylases inhibitors and the role of epigenetics in the development of diabetes [35]. It has to be emphasized that, in recent studies, it is reported that the amount of butyrate producers such as Roseburia species and Faecalibacterium prausnitzii is lower in patients affected with T2DM [11, 36].…”

Timing of complementary feeding is associated with gut microbiota diversity and composition and short chain fatty acid concentrations over the first year of life

“…The SCFA butyric acid (i.e. butyrate), in particular, is used as energy by colonocytes to maintain the mucosal barrier [15,21,22] and can regulate the expression of genes related to glucose metabolism [23]. Higher concentrations of butyrate and other SCFAs in the stool, however, may indicate that these metabolites are being excreted rather than absorbed [24].…”

Sodium Butyrate Protects ­Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice

“…Very recently, histone deacetylases and histone acetyltransferases are among the most important components in the modulation of pathological conditions in both diabetes and heart failure [Olson et al, ; Khan and Jena, ]. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) have emerged as crucial factors in the developing process of cardiac disorders with diverse etiologies [Sun et al, ; Kurdi and Booz, ].…”