Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice.

ABSTRACT: Although Hedgehog (Hh) signaling regulates cell differentiation during pancreas organogenesis, the consequences of pathway up-regulation in adult β-cells in vivo have not been investigated. Here, we elevate Hh signaling in β-cells by expressing an active version of the GLI2 transcription factor, a mediator of the Hh pathway, in β-cells that are also devoid of primary cilia, a critical regulator of Hh activity. We show that increased Hh signaling leads to impaired β-cell function and insulin secretion, resulting in glucose intolerance in transgenic mice. This phenotype was accompanied by reduced expression of both genes critical for β-cell function and transcription factors associated with their mature phenotype. Increased Hh signaling further correlated with increased expression of the pre

SUBMITTER: Landsman L 

PROVIDER: S-EPMC3193206 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature