Fig 6.

An integrated model displays a critical role of SIRT1 in maintaining PDX1 expression and β-cell formation. (A) SIRT1 interacts with, and deacetylates FOXA2 on the promoter of PDX1 and serves as a potent regulator for expression of PDX1 and its downstream genes during the early stages of pancreatic development and β-cell formation. Concurrently, expression of SIRT1 is also subjected to spatial and temporal regulation. (B) Targeted disruption of SIRT1 increases the acetylated form of FOXA2, impairs PDX1 expression, and blocks β-cell formation, leading to hyperglycemia and insulin insufficiency.