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Nasteska, D.* ; Fine, N.H.F.* ; Ashford, F.B.* ; Cuozzo, F.* ; Viloria, K.* ; Smith, G.* ; Dahir, A.* ; Dawson, P.W.J.* ; Lai, Y.C.* ; Bastidas-Ponce, A. ; Bakhti, M. ; Rutter, G.A.* ; Fiancette, R.* ; Nano, R.* ; Piemonti, L.* ; Lickert, H. ; Zhou, Q.* ; Akerman, I.* ; Hodson, D.J.*

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

Nat. Commun. 12:674 (2021)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Pancreatic-islets; Glucose-homeostasis; Negative Regulator; Ca2+ Oscillations; Heterogeneity; Secretion; Subpopulations; Dynamics; Identification; Dysfunction
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 674 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Förderungen Wellcome Trust
Medical Research Council