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Title

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

Authors
Gupta, Simone
Miyatsuka, Takeshi
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Published in Nature Cell Biology. 2018, vol. 20, no. 11, p. 1267-1277
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 is an active process mediated by repressive signals, which are released by neighbouring cells and curb an intrinsic trend of differentiated cells to change.
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PMID: 30361701
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Article (Published version) (2.6 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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CIGLIOLA, Valentina et al. Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon+ α-cells. In: Nature Cell Biology, 2018, vol. 20, n° 11, p. 1267-1277. https://archive-ouverte.unige.ch/unige:111714

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Deposited on : 2018-12-03

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