Impact of islet architecture on β-cell heterogeneity, plasticity and function
- 2 September 2016
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Endocrinology
- Vol. 12 (12), 695-709
- https://doi.org/10.1038/nrendo.2016.147
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.Keywords
This publication has 145 references indexed in Scilit:
- Sympathetic Innervation during Development Is Necessary for Pancreatic Islet Architecture and Functional MaturationCell Reports, 2013
- Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose HomeostasisCell Reports, 2012
- A local glucagon-like peptide 1 (GLP-1) system in human pancreatic isletsDiabetologia, 2012
- Innervation Patterns of Autonomic Axons in the Human Endocrine PancreasCell Metabolism, 2011
- The FoxA factors in organogenesis and differentiationCurrent Opinion in Genetics & Development, 2010
- Single pancreatic beta cells co-express multiple islet hormone genes in miceDiabetologia, 2009
- LKB1 Regulates Pancreatic β Cell Size, Polarity, and FunctionCell Metabolism, 2009
- The Ectopic Expression of Pax4 in the Mouse Pancreas Converts Progenitor Cells into α and Subsequently β CellsCell, 2009
- Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreasJournal of Molecular Histology, 2008
- Pancreatic innervation in mouse development and β-cell regenerationNeuroscience, 2007