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.
			
			
				
			
		 
		
			
				
					
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        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
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2021
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2021
    
 
    
    
        ISSN (print) / ISBN
        2041-1723
    
 
    
        e-ISSN
        2041-1723
    
 
    
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	    Band: 12,  
	    Heft: 1,  
	    Seiten: ,  
	    Artikelnummer: 674 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Nature Publishing Group
        
 
        
            Verlagsort
            London
        
 
	
        
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            0000-00-00
        
 
        
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        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