Regulation of β-cell-specific and glucose-dependent MafA expression

MafA, a basic-leucine zipper transcription factor that is important to pancreatic β-cell function, is regulated by several intricate mechanisms. MafA undergoes extensive post-translational modification by phosphorylation, ubiquitination and sumoylation, and these modifications regulate the turnover, DNA binding and transactivation function of the protein. Regulation of MafA expression is equally complex. The initial characterization of the β-cell specific MafA promoter identified six conserved sequence domains. One of these regions in particular contains consensus motifs and binding sites for several β-cell enriched transcription factors which ultimately play critical roles in controlling the expression of the gene. Interestingly, in cell culture, acute high glucose stimulation induces the accumulation of MafA, and MafA, in turn, regulates β-cell function. However, under chronic high glucose conditions, which occurs in the context of the diabetic state, β-cell function and, coincidentally, MafA levels decline. Currently, the mechanisms controlling the glucose-dependent accumulation of MafA are not well understood. This commentary highlights a recent report that further defines the regulation of β-cell-specific MafA expression and confirms the longstanding assumption that MafA transcription is upregulated in β-cells acutely cultured in high glucose, similar to what may occur in vivo under normoglycemic conditions.