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)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Pancreatic-islets; Glucose-homeostasis; Negative Regulator; Ca2+ Oscillations; Heterogeneity; Secretion; Subpopulations; Dynamics; Identification; Dysfunction
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 12,
Heft: 1,
Seiten: ,
Artikelnummer: 674
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
90000 - German Center for Diabetes Research
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-501900-231
G-502300-001
Förderungen
Wellcome Trust
Medical Research Council
Copyright
Erfassungsdatum
2021-04-12