Butyrate-Mediated Upregulation of Insulin Pathway Gene Expression Suggests Potential Antidiabetic Effects

Type 2 diabetes (T2D) is a major cause of morbidity in developed countries and involves insulin resistance, a failure to correctly respond to insulin. Numerous studies in rodent T2D models suggested that the short-chain fatty acid butyrate, produced by gut microbiota species through fermentation of dietary fibers, improves T2D symptoms. Here, we explored the potential antidiabetic effects of butyrate by measuring the transcription of selected T2D-implicated genes in human B lymphocyte-derived lymphoblastoid cell lines (LCLs) from 17 unrelated adult healthy donors. Human LCLs were cultured with and without sodium butyrate (1 mM for 48 h), followed by RNA extraction and real-time PCR analysis of the selected T2D-related genes. Butyrate significantly upregulated the expression of MT2A, RRAGD, IGF1R, OXTR, and INSR, while no changes were observed in the expression of other selected genes implicated in insulin signaling. Our findings, which should be considered preliminary until demonstrated by in vivo T2D animal models, suggest that butyrate is a potential modulator of metabolic pathways relevant to insulin resistance. Future studies should explore the tentative therapeutic potential of butyrate and its upregulated genes using proteomics and metabolomics in relevant tissues of T2D animal models, possibly followed by controlled clinical trials.