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PDX1LOW MAFALOW β-cells contribute to islet function and insulin release.

Authors :
Nasteska, Daniela
Fine, Nicholas H. F.
Ashford, Fiona B.
Cuozzo, Federica
Viloria, Katrina
Smith, Gabrielle
Dahir, Aisha
Dawson, Peter W. J.
Lai, Yu-Chiang
Bastidas-Ponce, Aimée
Bakhti, Mostafa
Rutter, Guy A.
Fiancette, Remi
Nano, Rita
Piemonti, Lorenzo
Lickert, Heiko
Zhou, Qiao
Akerman, Ildem
Hodson, David J.
Source :
Nature Communications; 1/29/2021, Vol. 12 Issue 1, p1-19, 19p
Publication Year :
2021

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 PDX1<superscript>HIGH</superscript> and MAFA<superscript>HIGH</superscript> β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1<superscript>HIGH</superscript> and MAFA<superscript>HIGH</superscript> 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 Ca<superscript>2+</superscript> 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. Beta cell subpopulations with low expression in PDX1, MAFA, and insulin might contribute to islet function and insulin release. Here the authors show that altering the proportion of PDX1<superscript>LOW</superscript> MAFA<superscript>LOW</superscript> to PDX1<superscript>HIGH</superscript> MAFA<superscript>HIGH</superscript> cells impairs islet function. [ABSTRACT FROM AUTHOR]

Subjects

Subjects :
INSULIN
PANCREATIC beta cells
GENES

Details

Language :
English
ISSN :
20411723
Volume :
12
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
148404946
Full Text :
https://doi.org/10.1038/s41467-020-20632-z