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

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Item Type:	Article
Title:	Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon(+) α-cells.
Creators Name:	Cigliola, V., Ghila, L., Thorel, F., van Gurp, L., Baronnier, D., Oropeza, D., Gupta, S., Miyatsuka, T., Kaneto, H., Magnuson, M.A., Osipovich, A.B., Sander, M., Wright, C.E.V., Thomas, M.K., Furuyama, K., Chera, S. and Herrera, P.L.
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.
Keywords:	Cell Lineage, Endocrinology, Insulin Signalling, Animals, Mice
Source:	Nature Cell Biology
ISSN:	1465-7392
Publisher:	Nature Publishing Group
Volume:	20
Number:	11
Page Range:	1267-1277
Date:	November 2018
Additional Information:	Copyright © The Author(s), under exclusive licence to Springer Nature Limited 2018
Official Publication:	https://doi.org/10.1038/s41556-018-0216-y
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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