Transcriptional mechanisms of pancreatic 13-cell maturation and functional adaptation

Pancreatic beta-cells secrete insulin commensurate to circulating nutrient levels to maintain normoglycemia. The ability of beta-cells to couple insulin secretion to nutrient stimuli is acquired during a postnatal maturation process. In mature beta-cells the insulin secretory response adapts to changes in nutrient state. Both beta-cell maturation and functional adaptation rely on the interplay between extracellular cues and cell type-specific transcriptional programs. Here we review emerging evidence that developmental and homeostatic regulation of beta-cell function involves collaboration between lineage-determining and signal-dependent transcription factors (LDTFs and SDTFs, respectively). A deeper understanding of beta-cell SDTFs and their cognate signals would delineate mechanisms of beta-cell maturation and functional adaptation, which has direct implications for diabetes therapies and for generating mature beta-cells from stem cells.