chapter  4
Role of Pdx-1 in β-Cell Growth
Pages 18

PDX-1 is a homeodomain transcription factor that acts as a key regulator of pancreas development, pancreatic β-cell differentiation, and β-cell function. It is one of the earliest markers of pancreatic morphogenesis, and its expression is maintained through­ out the life of the pancreatic β cell, indicating a role in β-cell function. As such, it is essential for pancreatic morphogenesis, and therefore, mutations in Pdx-1 form the basis for pancre­ atic agenesis in humans and mice. Its critical role in the differentiated insulin-producing β cell is underscored by its identification as a locus for human maturity onset diabetes of the young 4 (MODY4) and Type 2 diabetes. PDX-1 is an important transactivator of a number of β-cell genes, and experimental models of Pdx-1 reduction have demonstrated deficits in insulin expression and insulin secretion. Similarly, PDX-1 control of β-cell mass via β-cell proliferation and apoptosis has been supported by rodent models of diabetes. The study of PDX-1 and its mechanisms of action will not only inform our understanding of pancreatic development and function, but also provide insight into the pathogenesis of diabetes and novel avenues for treatment.