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Nat Rev Endocrinol. 2016 Dec;12(12):695-709. doi: 10.1038/nrendo.2016.147. Epub 2016 Sep 2.

Impact of islet architecture on β-cell heterogeneity, plasticity and function.

Author information

1
Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
2
German Center for Diabetes Research, 85764 Neuherberg, Germany.
3
Institute of Stem Cell Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
4
Technische Universität München, 81675 München, Germany.

Abstract

Although β-cell heterogeneity was discovered more than 50 years ago, the underlying principles have been explored only during the past decade. Islet-cell heterogeneity arises during pancreatic development and might reflect the existence of distinct populations of progenitor cells and the developmental pathways of endocrine cells. Heterogeneity can also be acquired in the postnatal period owing to β-cell plasticity or changes in islet architecture. Furthermore, β-cell neogenesis, replication and dedifferentiation represent alternative sources of β-cell heterogeneity. In addition to a physiological role, β-cell heterogeneity influences the development of diabetes mellitus and its response to treatment. Identifying phenotypic and functional markers to discriminate distinct β-cell subpopulations and the mechanisms underpinning their regulation is warranted to advance current knowledge of β-cell function and to design novel regenerative strategies that target subpopulations of β cells. In this context, the Wnt/planar cell polarity (PCP) effector molecule Flattop can distinguish two unique β-cell subpopulations with specific transcriptional signatures, functional properties and differential responses to environmental stimuli. In vivo targeting of these β-cell subpopulations might, therefore, represent an alternative strategy for the future treatment of diabetes mellitus.

PMID:
27585958
DOI:
10.1038/nrendo.2016.147

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