Hypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia

Abstract

In order to identify epigenetic mechanisms through which hyperglycemia can affect gene expression durably in β cells, we screened DNA methylation changes induced by high glucose concentrations (25 mmol/L) in the BTC3 murine cell line, using an epigenome‐wide approach. Exposure of BTC3 cells to high glucose modified the expression of 1612 transcripts while inducing significant methylation changes in 173 regions. Among these 173 glucose‐sensitive differentially methylated regions (DMRs), 14 were associated with changes in gene expression, suggesting an epigenetic effect of high glucose on gene transcription at these loci. Among these 14 DMRs, we selected for further study Pp2ac, a gene previously suspected to play a role in β‐cell physiology and type 2 diabetes. Using RT‐qPCR and bisulfite pyrosequencing, we confirmed our previous observations in BTC3 cells and found that this gene was significantly demethylated in the whole blood cells (WBCs) of type 2 diabetic patients compared to controls.

Comparative analysis of gene expression profiles in children with type 1 diabetes mellitus

“…Recently, CISH has emerged as an important modulator of β-cell insulin desensitization following prolonged glucose exposure. It has been reported that the expression and DNA methylation of CISH alter in response to hyperglycemia (22). Furthermore, the expression of CISH proteins is upregulated in islet cells from patients with T1D compared with healthy individuals (23).…”