| Activation of the Jak/Stat Signalling Pathway by Leukaemia Inhibitory Factor Stimulates Trans-differentiation of Human Non-Endocrine Pancreatic Cells into Insulin-Producing Cells. | |
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MedLine Citation:
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PMID: 22849859 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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T Koblas; I Leontovyč; K Zacharovová; Z Berková; J Kříž; P Girman; F Saudek |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Folia biologica Volume: 58 ISSN: 0015-5500 ISO Abbreviation: Folia Biol. (Praha) Publication Date: 2012 |
Date Detail:
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Created Date: 2012-08-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0234640 Medline TA: Folia Biol (Praha) Country: Czech Republic |
Other Details:
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Languages: eng Pagination: 98-105 Citation Subset: IM |
Affiliation:
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Institute for Clinical and Experimental Medicine, Prague, Czech Republic. |
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