Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon⁺ α-cells.

ABSTRACT: The mechanisms that restrict regeneration and maintain cell identity following injury are poorly characterized in higher vertebrates. Following β-cell loss, 1-2% of the glucagon-producing α-cells spontaneously engage in insulin production in mice. Here we explore the mechanisms inhibiting α-cell plasticity. We show that adaptive α-cell identity changes are constrained by intra-islet insulin- and Smoothened-mediated signalling, among others. The combination of β-cell loss or insulin-signalling inhibition, with Smoothened inactivation in α- or δ-cells, stimulates insulin production in more α-cells. These findings suggest that the removal of constitutive 'brake signals' is crucial to neutralize the refractoriness to adaptive cell-fate changes. It appears that the maintenance of cell identity

SUBMITTER: Cigliola V 

PROVIDER: S-EPMC6215453 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature