Document Detail


Activation of the Jak/Stat Signalling Pathway by Leukaemia Inhibitory Factor Stimulates Trans-differentiation of Human Non-Endocrine Pancreatic Cells into Insulin-Producing Cells.
MedLine Citation:
PMID:  22849859     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Differentiation of pancreatic β-cells is regulated by a wide range of signalling pathways. The aim of our current work was to evaluate the effect of the Jak/Stat signalling pathway on the differentiation of human non-endocrine pancreatic cells into insulin-producing cells. Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor (LIF) stimulated differentiation of C-peptide-negative human non-endocrine pancreatic cells into insulin-producing cells in 6.3 ± 2.0 % cells (N = 5) and induced expression of pro-endocrine transcription factor neurogenin 3, Notch signalling pathway suppressor HES6 and stimulator of β-cell neogenesis REG3A. The expression of the REG3A gene and increased rate of differentiation into insulin-producing cells (10.2 ± 2.1 %) were further stimulated by a combination of LIF with nicotinamide and dexamethasone. Glucose-stimulated (5 vs. 20 mM) C-peptide secretion confirmed proper insulin secretory function of trans-differentiated insulin-producing cells (0.51 vs. 2.03 pmol C-peptide/μg DNA, P < 0.05). Our results indicate that Jak/Stat signalling critically contributes to trans-differentiation of non-endocrine pancreatic cells into functional insulin-producing cells. The positive effect of the Jak/Stat signalling pathway on trans-differentiation is mediated by the key genes that activate differentiation of pancreatic β-cells.
Authors:
T Koblas; I Leontovyč; K Zacharovová; Z Berková; J Kříž; P Girman; F Saudek
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Folia biologica     Volume:  58     ISSN:  0015-5500     ISO Abbreviation:  Folia Biol. (Praha)     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0234640     Medline TA:  Folia Biol (Praha)     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  98-105     Citation Subset:  IM    
Affiliation:
Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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