Beta-cell dysfunction induced by non-cytotoxic concentrations of Interleukin-1β is associated with changes in expression of beta-cell maturity genes and associated histone modifications

Item Type:	Article
Title:	Beta-cell dysfunction induced by non-cytotoxic concentrations of Interleukin-1β is associated with changes in expression of beta-cell maturity genes and associated histone modifications
Creators Name:	Ibarra Urizar, A. and Prause, M. and Wortham, M. and Sui, Y. and Thams, P. and Sander, M. and Christensen, G.L. and Billestrup, N.
Abstract:	Decreased insulin secretory capacity in Type 2 diabetes mellitus is associated with beta-cell dedifferentiation and inflammation. We hypothesize that prolonged exposure of beta-cells to low concentrations of IL-1β induce beta-cell dedifferentiation characterized by impaired glucose-stimulated insulin secretion, reduced expression of key beta-cell genes and changes in histone modifications at gene loci known to affect beta-cell function. Ten days exposure to IL-1β at non-cytotoxic concentrations reduced insulin secretion and beta-cell proliferation and decreased expression of key beta-cell identity genes, including MafA and Ucn3 and decreased H3K27ac at the gene loci, suggesting that inflammatory cytokines directly affects the epigenome. Following removal of IL-1β, beta-cell function was normalized and mRNA expression of beta-cell identity genes, such as insulin and Ucn3 returned to pre-stimulation levels. Our findings indicate that prolonged exposure to low concentrations of IL-1β induces epigenetic changes associated with loss of beta-cell identity as observed in Type 2 diabetes.
Keywords:	Type 2 Diabetes Mellitus, Genetic Epigenesis, Gene Expression Regulation, Histones, Insulin-Secreting Cells, Interleukin-1beta, Large Maf Transcription Factors, Post-Translational Protein Processing, Urocortins, Animals, Mice
Source:	Molecular and Cellular Endocrinology
ISSN:	0303-7207
Publisher:	Elsevier
Volume:	496
Page Range:	110524
Date:	1 October 2019
Official Publication:	https://doi.org/10.1016/j.mce.2019.110524
PubMed:	View item in PubMed

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