| Literature DB >> 33514698 |
Daniela Nasteska1,2,3, Nicholas H F Fine1,2,3, Fiona B Ashford1,2,3, Federica Cuozzo1,2,3, Katrina Viloria1,2,3, Gabrielle Smith1,3, Aisha Dahir1,3, Peter W J Dawson4,5, Yu-Chiang Lai1,4,5, Aimée Bastidas-Ponce6,7,8,9, Mostafa Bakhti6,7,8, Guy A Rutter10,11, Remi Fiancette12, Rita Nano13,14, Lorenzo Piemonti13,14, Heiko Lickert6,7,8,9, Qiao Zhou15, Ildem Akerman1,3, David J Hodson16,17,18.
Abstract
Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in β-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and MAFAHIGH β-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca2+ signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the β-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in β-cell maturity, might be important for the maintenance of islet function.Entities:
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Year: 2021 PMID： 33514698 PMCID： PMC7846747 DOI： 10.1038/s41467-020-20632-z
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919