Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell.

ABSTRACT: Foxa1 and Foxa2 play both redundant and distinct roles in early pancreas development. We demonstrate here that inducible ablation of both transcription factors in mature mouse beta-cells leads to impaired glucose homeostasis and insulin secretion. The defects in both glucose-stimulated insulin secretion and intracellular calcium oscillation are more pronounced than those in beta-cells lacking only Foxa2. Unexpectedly, in contrast to the severe reduction of beta-cell-enriched factors contributing to metabolic and secretory pathways, expression of a large number of genes that are involved in neural differentiation and function is significantly elevated. We further demonstrate that expression of carbohydrate response element-binding protein (ChREBP or Mlxipl), an important transcriptional reg

SUBMITTER: Gao N 

PROVIDER: S-EPMC2940470 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature