Ultrastructure characterization of pancreatic β-cells is accompanied by modulatory effects of the HDAC inhibitor sodium butyrate on the PI3/AKT insulin signaling pathway in juvenile diabetic rats

Epigenetic modifications in pancreas development, diabetes, and therapeutics

“…It has been proposed for the treatment of juvenile diabetes (especially T1D) based on the observation that it improves glucose homeostasis by improving β cells proliferation and function, decreasing β cells apoptosis, and modulating the p38/ERK MAPK pathway. Treatment with NaB results in significant improvement in plasma glucose levels, plasma insulin levels/expression, ameliorated diabetes‐induced histological alternations, and increased the expression of phosphorylated AKT 149 . It also induces nuclear‐encoded mitochondrial genes for −1 nucleosome repositioning and causes muscle mitochondrial adaptations in skeletal muscles.…”

“…However, treatment with BRD3308, an Hdac3 inhibitor, protected rats against T1D by reducing immune cell infiltration into pancreatic islets suggesting a role for HDACs in the establishment of self‐tolerance 51 . Treatment with HDAC inhibitors such as sodium butyrate (NaB) and N‐(2‐amino‐phenyl)‐4‐(4‐pyridin‐3‐yl‐pyrimidin‐2‐ylamino)‐methyl)‐benzamide (MGCD0103) has been found effective in improving blood glucose and insulin levels in STZ‐induced diabetic rat models 52–54 …”

“… 51 Treatment with HDAC inhibitors such as sodium butyrate (NaB) and N‐(2‐amino‐phenyl)‐4‐(4‐pyridin‐3‐yl‐pyrimidin‐2‐ylamino)‐methyl)‐benzamide (MGCD0103) has been found effective in improving blood glucose and insulin levels in STZ‐induced diabetic rat models. 52 , 53 , 54 …”

“…Treatment with NaB results in significant improvement in plasma glucose levels, plasma insulin levels/expression, ameliorated diabetes‐induced histological alternations, and increased the expression of phosphorylated AKT. 149 It also induces nuclear‐encoded mitochondrial genes for −1 nucleosome repositioning and causes muscle mitochondrial adaptations in skeletal muscles. Treatment with NaB eventually leads to improved β‐oxidation and a lean, insulin‐sensitive phenotype.…”

The role and mechanism of butyrate in the prevention and treatment of diabetic kidney disease

“…Among these SCFAs, butyrate is of particular concern due to its positive influence on cell energy metabolism and intestinal environmental stability ( Guilloteau et al, 2010 ). It also relieves oxidative stress, inflammation, and fibrosis in diabetes and kidney diseases via G-protein coupled receptors (GPCRs) or serves as an epigenetic regulator by inhibiting histone deacetylase (HDAC), up-regulation of miRNAs, or induction of the histone butyrylation, a novel histone post-translational modification ( Lin et al, 2015 ; Lu et al, 2016 ; Xu et al, 2018 ; Gonzalez et al, 2019 ; Sanna et al, 2019 ; Elgamal et al, 2020 ; Noureldein et al, 2020 ; Rodríguez-Carlos et al, 2020 ). Studies have already reported the therapeutic effects of butyrate or sodium butyrate, demonstrating that butyrate metabolic pathway could be a new therapeutic target for DKD ( Du et al, 2020a , b ; Huang et al, 2020 ; Li et al, 2020 ).…”