Pancreatic β cells support glucose homeostasis with great precision by matching insulin release to the metabolic needs of the moment. Previous gene-expression analysis indicates that adult β cells not only produce cell-specific proteins, but also repress a small set of housekeeping genes — such as those encoding lactate dehydrogenase A (LDHA), solute transporter MCT1, and hexokinase 1 (HK1) — that would otherwise interfere with normal β cell function. In this issue of the JCI, Dhawan et al. elucidate a molecular mechanism involved in β cell–specific repression of
DNMT3A mediates repression of genes that disrupt normal glucose-regulated insulin release in β cells.