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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

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@article{a4794525a0d9412cb57fda4b85f51431,
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",
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.",
author = "{Ibarra Urizar}, Adriana and Michala Prause and Matthew Wortham and Yinghui Sui and Peter Thams and Maike Sander and Christensen, {Gitte Lund} and Nils Billestrup",
note = "Copyright {\circledC} 2019 Elsevier B.V. All rights reserved.",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.mce.2019.110524",
language = "English",
volume = "496",
pages = "110524",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - 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

AU - Ibarra Urizar, Adriana

AU - Prause, Michala

AU - Wortham, Matthew

AU - Sui, Yinghui

AU - Thams, Peter

AU - Sander, Maike

AU - Christensen, Gitte Lund

AU - Billestrup, Nils

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.mce.2019.110524

DO - 10.1016/j.mce.2019.110524

M3 - Review

VL - 496

SP - 110524

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -

ID: 59692672